Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology

A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition,...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in immunology Vol. 9; p. 2486
Main Authors Watanabe, Keisuke, Kuramitsu, Shunichiro, Posey, Jr, Avery D, June, Carl H
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 26.10.2018
Subjects
Animals
Antigens, Neoplasm - immunology
cancer immunology
chimeric antigen receptors
Humans
immune synapse formation
Immunological Synapses - metabolism
Immunology
immunotherapy
Immunotherapy, Adoptive - methods
Neoplasms - immunology
Neoplasms - therapy
Receptors, Antigen, T-Cell - genetics
T cell biology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
T cell biology
chimeric antigen receptors
immune synapse formation
cancer immunology
immunotherapy
Online AccessGet full text

Cover

Abstract A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells. In this review, we discuss the recent findings of mechanisms of antigen recognition through CAR, including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions. We also discuss rational strategies to adjust and expand the therapeutic window for effective and safe targeting of solid tumors by CAR T cell platforms.
AbstractList A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells. In this review, we discuss the recent findings of mechanisms of antigen recognition through CAR, including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions. We also discuss rational strategies to adjust and expand the therapeutic window for effective and safe targeting of solid tumors by CAR T cell platforms.
A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells. In this review, we discuss the recent findings of mechanisms of antigen recognition through CAR, including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions. We also discuss rational strategies to adjust and expand the therapeutic window for effective and safe targeting of solid tumors by CAR T cell platforms.A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells. In this review, we discuss the recent findings of mechanisms of antigen recognition through CAR, including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions. We also discuss rational strategies to adjust and expand the therapeutic window for effective and safe targeting of solid tumors by CAR T cell platforms.
Author Watanabe, Keisuke
Posey, Jr, Avery D
Kuramitsu, Shunichiro
June, Carl H
AuthorAffiliation 4 Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA , United States
1 Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA , United States
3 Corporal Michael J. Crescenz VA Medical Center , Philadelphia, PA , United States
2 Parker Institute for Cancer Immunotherapy, University of Pennsylvania , Philadelphia, PA , United States
AuthorAffiliation_xml – name: 4 Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA , United States
– name: 1 Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA , United States
– name: 2 Parker Institute for Cancer Immunotherapy, University of Pennsylvania , Philadelphia, PA , United States
– name: 3 Corporal Michael J. Crescenz VA Medical Center , Philadelphia, PA , United States
Author_xml – sequence: 1
  givenname: Keisuke
  surname: Watanabe
  fullname: Watanabe, Keisuke
  organization: Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
– sequence: 2
  givenname: Shunichiro
  surname: Kuramitsu
  fullname: Kuramitsu, Shunichiro
  organization: Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
– sequence: 3
  givenname: Avery D
  surname: Posey, Jr
  fullname: Posey, Jr, Avery D
  organization: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States
– sequence: 4
  givenname: Carl H
  surname: June
  fullname: June, Carl H
  organization: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30416506$$D View this record in MEDLINE/PubMed
BookMark eNpVkUtvEzEUhS1UREvpnhXykk2C3zNmgVSiAhWVkCAVS8sZ30lcZuzUnmnJv8d5UKXe-HHP-ezr8xqdhBgAobeUTDmv9YfW9_04ZYTWU8JErV6gM6qUmHDGxMnR-hRd5HxHyhCacy5foVNOBFWSqDP0cPV3bYPzYYmHFeD5CpJdwzj4Bv_2wcVH3MaEZ5c_8RzPoOsOig32Af-KnXd4PvYx5Y_bAv4e4mPIuADxbfiz38T22P7Zxy4uN2_Qy9Z2GS4O8zm6_XI1n32b3Pz4ej27vJk0kuhhop2yUljFua2rymrJNLMtyIYK0tSaVkI4wSiVSoDjxKqFJRXRrrFcattW_Bxd77ku2juzTr63aWOi9WZ3ENPS2FSa7cAAEwRaUoECISStF4oUPmc1UKXJghTWpz1rPS56cA2EIdnuGfR5JfiVWcYHoxhlUm4B7w-AFO9HyIPpfW7Kr9gAccyG0RKXLg3QIiV7aZNizgnap2soMdv0zS59s03f7NIvlnfHz3sy_M-a_wNa9qvO
CitedBy_id crossref_primary_10_3389_fimmu_2022_994532
crossref_primary_10_1016_j_ctrv_2020_102089
crossref_primary_10_1080_1354750X_2021_2016973
crossref_primary_10_1002_onco_13575
crossref_primary_10_7554_eLife_58065
crossref_primary_10_7554_eLife_74272
crossref_primary_10_1016_j_ccell_2021_12_005
crossref_primary_10_3390_ijms232314563
crossref_primary_10_3389_fmolb_2022_849363
crossref_primary_10_1038_s41551_021_00781_2
crossref_primary_10_1016_j_cellimm_2020_104069
crossref_primary_10_3390_antib8030041
crossref_primary_10_1186_s40364_020_0183_x
crossref_primary_10_1177_15330338221118413
crossref_primary_10_3389_fbioe_2023_1101122
crossref_primary_10_1177_09636897221094244
crossref_primary_10_1001_jamaoncol_2021_0168
crossref_primary_10_1007_s13770_022_00515_8
crossref_primary_10_1038_s41417_020_0183_x
crossref_primary_10_1158_1535_7163_MCT_20_1030
crossref_primary_10_3389_fimmu_2022_1032403
crossref_primary_10_3390_cancers12010125
crossref_primary_10_3389_fimmu_2021_600829
crossref_primary_10_15789_10_15789_1563_0625_MTC_2444
crossref_primary_10_3389_fimmu_2022_822004
crossref_primary_10_1158_1535_7163_MCT_21_0872
crossref_primary_10_1038_s41375_023_01976_z
crossref_primary_10_1080_10428194_2020_1761967
crossref_primary_10_3390_ijms222111694
crossref_primary_10_1038_s41590_023_01659_y
crossref_primary_10_1111_bcp_14281
crossref_primary_10_1016_j_lfs_2023_122387
crossref_primary_10_3390_ijms22052476
crossref_primary_10_1016_j_actbio_2020_04_015
crossref_primary_10_3390_cells12182261
crossref_primary_10_3389_fimmu_2020_01792
crossref_primary_10_1038_s41598_019_48711_2
crossref_primary_10_1158_2326_6066_CIR_21_0536
crossref_primary_10_1186_s13287_020_02128_1
crossref_primary_10_1126_science_aax4556
crossref_primary_10_1002_cam4_5551
crossref_primary_10_1007_s00262_020_02692_8
crossref_primary_10_1080_2162402X_2019_1684127
crossref_primary_10_3389_fimmu_2022_871661
crossref_primary_10_1146_annurev_cancerbio_030419_033657
crossref_primary_10_1016_j_jcyt_2022_03_008
crossref_primary_10_1038_s41586_023_06243_w
crossref_primary_10_3390_cancers15041052
crossref_primary_10_3389_fcell_2019_00370
crossref_primary_10_3390_jcm11082158
crossref_primary_10_3389_fimmu_2022_835762
crossref_primary_10_1126_scitranslmed_aba7308
crossref_primary_10_3390_ijms23136931
crossref_primary_10_3389_fimmu_2021_782448
crossref_primary_10_1038_s41587_022_01650_2
crossref_primary_10_1080_19420862_2019_1688616
crossref_primary_10_1080_14712598_2019_1595582
crossref_primary_10_1136_jitc_2022_004854
crossref_primary_10_1016_j_heliyon_2022_e09577
crossref_primary_10_3389_fimmu_2022_850358
crossref_primary_10_3390_jcm9010182
crossref_primary_10_1016_j_ymthe_2020_06_004
crossref_primary_10_1007_s11864_020_00772_6
crossref_primary_10_1016_j_addr_2022_114358
crossref_primary_10_1111_imr_12796
crossref_primary_10_1186_s13045_019_0813_7
crossref_primary_10_3390_pharmaceutics15102458
crossref_primary_10_1038_s41577_019_0195_7
crossref_primary_10_1089_thy_2019_0604
crossref_primary_10_1111_imm_13187
crossref_primary_10_3389_fimmu_2020_565236
crossref_primary_10_1016_j_bpj_2023_09_004
crossref_primary_10_3390_ijms20235942
crossref_primary_10_1073_pnas_2022410118
crossref_primary_10_3389_fimmu_2023_1213716
crossref_primary_10_1136_jitc_2023_008566
crossref_primary_10_1158_1078_0432_CCR_22_1379
crossref_primary_10_1016_j_biotechadv_2022_107917
crossref_primary_10_1016_j_blre_2020_100695
crossref_primary_10_1002_advs_202203106
crossref_primary_10_3389_fimmu_2023_1121973
crossref_primary_10_3390_ijms23137431
crossref_primary_10_1016_j_xcrm_2021_100449
crossref_primary_10_1007_s00432_021_03839_5
crossref_primary_10_1016_j_omto_2020_03_003
crossref_primary_10_1159_000500488
crossref_primary_10_1016_j_drudis_2021_01_002
crossref_primary_10_3390_cells10112940
crossref_primary_10_1016_j_neo_2022_100801
crossref_primary_10_3390_ijms21103525
crossref_primary_10_1016_j_medj_2022_05_001
crossref_primary_10_1016_j_lfs_2024_122556
crossref_primary_10_1111_ijd_14945
crossref_primary_10_1038_s41467_021_27853_w
crossref_primary_10_1002_bit_28753
crossref_primary_10_1126_sciimmunol_abd5515
crossref_primary_10_1038_s41423_020_0470_3
crossref_primary_10_3390_immuno1030010
crossref_primary_10_3389_fimmu_2024_1386856
crossref_primary_10_3390_cancers14040967
crossref_primary_10_3390_ijerph192416475
crossref_primary_10_1093_intimm_dxab052
crossref_primary_10_3389_fonc_2023_1168454
crossref_primary_10_1007_s00432_020_03260_4
crossref_primary_10_1016_j_immuni_2020_07_011
crossref_primary_10_3390_cells12131787
crossref_primary_10_3390_cells8111341
crossref_primary_10_1158_1078_0432_CCR_20_2448
crossref_primary_10_21320_2500_2139_2023_16_3_268_279
crossref_primary_10_3389_fimmu_2019_00661
crossref_primary_10_1080_2162402X_2022_2054106
crossref_primary_10_1111_trf_17030
crossref_primary_10_3390_ijms21020381
crossref_primary_10_3390_cancers12113329
crossref_primary_10_1158_1078_0432_CCR_19_1649
crossref_primary_10_1038_s41467_021_25605_4
crossref_primary_10_1111_1759_7714_14375
crossref_primary_10_1136_jitc_2021_003771
crossref_primary_10_1158_1535_7163_MCT_22_0073
crossref_primary_10_1158_1078_0432_CCR_19_0421
crossref_primary_10_1007_s13346_024_01572_3
crossref_primary_10_1182_bloodadvances_2022008490
crossref_primary_10_3390_cancers13040743
crossref_primary_10_1007_s12307_019_00233_1
crossref_primary_10_3390_ijms232214255
crossref_primary_10_1002_jcph_1691
crossref_primary_10_1038_s41551_020_00625_5
crossref_primary_10_1158_2326_6066_CIR_21_0853
crossref_primary_10_1158_2159_8290_CD_20_1638
crossref_primary_10_1016_j_tibtech_2021_12_009
crossref_primary_10_1080_21645515_2023_2172278
crossref_primary_10_1016_j_addr_2023_115135
crossref_primary_10_1007_s00018_019_03156_8
crossref_primary_10_3390_cancers13040867
crossref_primary_10_3389_fimmu_2021_619069
crossref_primary_10_3390_cancers12030683
crossref_primary_10_1038_s41587_020_0580_6
crossref_primary_10_1016_j_celrep_2023_112797
crossref_primary_10_3389_fimmu_2020_01109
crossref_primary_10_1186_s12964_020_00617_7
crossref_primary_10_1002_cac2_12330
crossref_primary_10_1007_s12026_022_09348_y
crossref_primary_10_3390_cancers14071627
crossref_primary_10_1016_j_critrevonc_2020_103096
crossref_primary_10_3390_immuno3020013
crossref_primary_10_1002_advs_202002628
crossref_primary_10_1038_s41420_024_01976_7
crossref_primary_10_3390_ijms25084170
crossref_primary_10_1002_adhm_202000275
crossref_primary_10_1038_s41571_019_0184_6
crossref_primary_10_1038_s41408_021_00469_5
crossref_primary_10_3389_fimmu_2021_638639
crossref_primary_10_1007_s11010_022_04568_0
crossref_primary_10_1016_j_biopha_2019_109625
crossref_primary_10_1038_s41577_021_00539_6
crossref_primary_10_1038_s41598_021_92196_x
crossref_primary_10_1002_med_21818
Cites_doi 10.1073/pnas.1221609110
10.1083/jcb.201008140
10.1073/pnas.86.24.10024
10.1002/eji.1830250432
10.1016/j.ymthe.2017.06.003
10.1002/eji.201242606
10.1200/JCO.2014.58.3377
10.1016/j.ymthe.2017.09.010
10.1038/mt.2011.286
10.1038/mt.2009.210
10.1111/j.1365-2567.2008.03015.x
10.1016/j.immuni.2016.05.014
10.1038/nbt.2459
10.1158/0008-5472.CAN-15-0159
10.1158/1078-0432.CCR-17-2041
10.1073/pnas.1420936111
10.1172/JCI83416
10.1038/nature01076
10.1084/jem.186.5.757
10.1093/glycob/cwj044
10.1158/2326-6066.CIR-13-0170
10.1038/sj.leu.2403302
10.1158/0008-5472.CAN-16-1831
10.1172/jci.insight.96976
10.1172/JCI84813
10.1038/cgt.2015.47
10.1073/pnas.1018771108
10.1073/pnas.1413726111
10.18632/oncotarget.9114
10.1016/j.immuni.2010.09.006
10.1038/mtna.2013.32
10.1158/1078-0432.CCR-17-0344
10.1038/375148a0
10.1038/mt.2011.256
10.1038/mt.2013.185
10.4049/jimmunol.1402346
10.1007/s12026-011-8204-3
10.1158/2326-6066.CIR-17-0211
10.1016/j.celrep.2017.09.002
10.1016/S1074-7613(01)00234-5
10.1038/mt.2010.24
10.1200/JCO.2014.56.2025
10.1016/j.ymthe.2017.04.024
10.1158/2326-6066.CIR-17-0189
10.1016/j.celrep.2017.09.015
10.4049/jimmunol.173.12.7647
10.4161/onci.20592
10.4049/jimmunol.176.12.7308
10.1038/mt.2010.272
10.1038/nbt.4086
10.1038/s41434-018-0007-x
10.1158/2326-6066.CIR-15-0048
10.1038/nm.4431
10.1158/1078-0432.CCR-15-0428
10.1016/j.ymthe.2016.10.011
10.1182/blood-2008-08-175208
10.1126/science.281.5376.572
10.1158/1078-0432.CCR-12-1449
10.1158/0008-5472.CAN-15-0139
10.1158/0008-5472.CAN-14-0697
10.1200/JCO.2006.05.9964
10.1158/1078-0432.CCR-13-0330
10.1016/j.immuni.2013.08.036
10.1158/2159-8290.CD-15-1020
10.1158/0008-5472.CAN-04-1525
10.1016/j.cell.2016.01.012
10.1016/j.cell.2016.09.011
10.1038/nbt.2725
10.1056/NEJMoa1215134
10.1016/j.ymthe.2018.01.020
10.4049/jimmunol.1001867
10.1038/leu.2010.75
10.1038/377032a0
10.4049/jimmunol.1000173
10.1056/NEJMoa1610497
10.1056/NEJMoa1106152
10.1158/2326-6066.CIR-14-0186
10.1097/CJI.0b013e3180de5d90
10.1158/2326-6066.CIR-17-0314
10.1056/NEJMoa1407222
10.4049/jimmunol.180.7.4901
10.1172/jci.insight.99573
10.1038/nature21405
10.4049/jimmunol.177.9.6548
10.4049/jimmunol.161.6.2791
10.1126/scitranslmed.aaa0984
10.1182/blood-2011-12-400044
10.1073/pnas.1716266115
10.1073/pnas.1221312110
10.1158/2326-6066.CIR-16-0043
10.1016/j.ymthe.2017.06.008
10.1038/s41598-017-14749-3
10.1007/s10875-012-9689-9
10.1016/j.cell.2017.01.016
10.1038/nchembio.2565
10.1158/0008-5472.CAN-11-3890
10.1038/nature05071
10.1182/blood-2013-03-490565
10.1158/2326-6066.CIR-14-0127
10.1038/nrc3770
10.1371/journal.pone.0144787
ContentType Journal Article
Copyright Copyright © 2018 Watanabe, Kuramitsu, Posey and June. 2018 Watanabe, Kuramitsu, Posey and June
Copyright_xml – notice: Copyright © 2018 Watanabe, Kuramitsu, Posey and June. 2018 Watanabe, Kuramitsu, Posey and June
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
5PM
DOA
DOI 10.3389/fimmu.2018.02486
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList MEDLINE

MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 1664-3224
ExternalDocumentID oai_doaj_org_article_e240ef07e6e44518b60174328e1690b0
10_3389_fimmu_2018_02486
30416506
Genre Research Support, U.S. Gov't, Non-P.H.S
Review
Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NCI NIH HHS
  grantid: R01 CA226983
– fundername: NCI NIH HHS
  grantid: P01 CA214278
– fundername: BLRD VA
  grantid: IK2 BX004183
GroupedDBID 53G
5VS
9T4
AAFWJ
AAKDD
ACGFO
ACGFS
ACXDI
ADBBV
ADRAZ
AENEX
AFPKN
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BCNDV
CGR
CUY
CVF
DIK
EBS
ECM
EIF
EMOBN
GROUPED_DOAJ
GX1
HYE
IAO
IEA
IHR
IHW
IPNFZ
KQ8
M48
M~E
NPM
OK1
PGMZT
RIG
RNS
RPM
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c509t-9d6a54a633a877a95292afe5c140c891744d4211564ed30a6ba0709dca359af73
IEDL.DBID RPM
ISSN 1664-3224
IngestDate Tue Oct 22 15:08:25 EDT 2024
Tue Sep 17 21:18:26 EDT 2024
Sun Oct 20 16:45:08 EDT 2024
Thu Sep 26 18:24:26 EDT 2024
Thu Oct 24 09:41:08 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords T cell biology
chimeric antigen receptors
immune synapse formation
cancer immunology
immunotherapy
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c509t-9d6a54a633a877a95292afe5c140c891744d4211564ed30a6ba0709dca359af73
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
Edited by: Salem Chouaib, Institut Gustave Roussy, France
Reviewed by: Maksim Mamonkin, Baylor College of Medicine, United States; Pappanaicken R. Kumaresan, University of Texas MD Anderson Cancer Center, United States
This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212550/
PMID 30416506
PQID 2132290701
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_e240ef07e6e44518b60174328e1690b0
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6212550
proquest_miscellaneous_2132290701
crossref_primary_10_3389_fimmu_2018_02486
pubmed_primary_30416506
PublicationCentury 2000
PublicationDate 2018-10-26
PublicationDateYYYYMMDD 2018-10-26
PublicationDate_xml – month: 10
  year: 2018
  text: 2018-10-26
  day: 26
PublicationDecade 2010
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
PublicationTitle Frontiers in immunology
PublicationTitleAlternate Front Immunol
PublicationYear 2018
Publisher Frontiers Media S.A
Publisher_xml – name: Frontiers Media S.A
References Posey (B54) 2016; 44
Lamers (B5) 2006; 24
Eyquem (B41) 2017; 543
Brown (B15) 2015; 21
Birnbaum (B7) 2014; 111
Engels (B53) 2012; 20
Hu (B91) 2017; 20
Nolan (B26) 1999; 5
Purbhoo (B42) 2006; 176
Suarez (B93) 2016; 7
Liu (B37) 2015; 75
Zhong (B47) 2013; 110
Valitutti (B48) 1995; 375
Isaaz (B38) 1995; 25
Caserta (B52) 2010; 185
Priceman (B86) 2018; 24
Choi (B39) 2013; 110
Wang (B78) 2018; 24
Parkhurst (B6) 2011; 19
Morsut (B102) 2016; 164
Guedan (B14) 2018; 3
Hiraga (B96) 2009; 113
Grada (B69) 2013; 2
Edwards (B50) 2011; 50
Chmielewski (B62) 2004; 173
Stinchcombe (B18) 2006; 443
O'Rourke (B56) 2017; 9
Turatti (B63) 2007; 30
Karlsson (B20) 2015; 10
Xiong (B22) 2018; 26
Stone (B49) 2009; 126
Schmid (B46) 2010; 184
Gomes-Silva (B66) 2017; 21
Di Stasi (B98) 2011; 365
Imai (B13) 2004; 18
Stinchcombe (B17) 2001; 15
Hegde (B71) 2016; 126
Davenport (B23) 2018; 115
Tchou (B88) 2017; 5
Davenport (B40) 2015; 3
Sakemura (B101) 2016; 4
Wing (B84) 2018; 6
Beatty (B100) 2014; 2
Rosewell Shaw (B83) 2017; 25
Hatada (B8) 1995; 377
Castellarin (B57) 2018; 25
Hosen (B55) 2017; 23
Au-Yeung (B32) 2014; 111
Pegram (B90) 2012; 119
Drent (B61) 2017; 25
Paszkiewicz (B99) 2016; 126
Zhong (B21) 2010; 18
Roybal (B103) 2016; 167
Morgan (B4) 2010; 18
Gross (B11) 1989; 86
Watanabe (B34) 2015; 194
Mukherjee (B24) 2017; 25
Watanabe (B81) 2018; 3
Itoh (B33) 1997; 186
Kloss (B68) 2013; 31
Caruso (B60) 2015; 75
Mardiana (B85) 2017; 77
Kersh (B9) 1998; 281
Nishio (B82) 2014; 74
Grupp (B1) 2013; 368
Tamada (B73) 2012; 18
Tsun (B19) 2011; 192
Irvine (B29) 2002; 419
Hudecek (B76) 2015; 3
Manz (B31) 2011; 108
Maude (B2) 2014; 371
Lanitis (B27) 2012; 20
Lichty (B80) 2014; 14
Hombach (B25) 1998; 58
Chang (B28) 2018; 14
Sorensen (B58) 2006; 16
Aleksic (B44) 2012; 42
Johnson (B45) 2006; 177
Urbanska (B72) 2012; 72
Park (B64) 2017; 7
Han (B89) 2017; 25
Richman (B51) 2018; 6
Finney (B12) 1998; 161
Frigault (B65) 2015; 3
Kochenderfer (B3) 2015; 33
Linette (B43) 2013; 122
Hinrichs (B59) 2013; 31
Kuramitsu (B77) 2015; 22
Yokosuka (B16) 2010; 33
Lim (B10) 2017; 168
Hoyos (B97) 2010; 24
Walker (B36) 2017; 25
Sotillo (B94) 2015; 5
Adachi (B92) 2018; 36
Garnett (B95) 2004; 64
Brown (B87) 2016; 375
Stone (B35) 2012; 1
Huang (B30) 2013; 39
Hudecek (B75) 2013; 19
Andtbacka (B79) 2015; 33
Wilkie (B74) 2008; 180
Wilkie (B67) 2012; 32
Hegde (B70) 2013; 21
References_xml – volume: 110
  start-page: 6973
  year: 2013
  ident: B47
  article-title: T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1221609110
  contributor:
    fullname: Zhong
– volume: 192
  start-page: 663
  year: 2011
  ident: B19
  article-title: Centrosome docking at the immunological synapse is controlled by Lck signaling
  publication-title: J Cell Biol.
  doi: 10.1083/jcb.201008140
  contributor:
    fullname: Tsun
– volume: 86
  start-page: 10024
  year: 1989
  ident: B11
  article-title: Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.86.24.10024
  contributor:
    fullname: Gross
– volume: 25
  start-page: 1071
  year: 1995
  ident: B38
  article-title: Serial killing by cytotoxic T lymphocytes: T cell receptor triggers degranulation, re-filling of the lytic granules and secretion of lytic proteins via a non-granule pathway
  publication-title: Eur J Immunol.
  doi: 10.1002/eji.1830250432
  contributor:
    fullname: Isaaz
– volume: 25
  start-page: 1757
  year: 2017
  ident: B24
  article-title: Quantitative imaging approaches to study the CAR immunological synapse
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2017.06.003
  contributor:
    fullname: Mukherjee
– volume: 42
  start-page: 3174
  year: 2012
  ident: B44
  article-title: Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies
  publication-title: Eur J Immunol.
  doi: 10.1002/eji.201242606
  contributor:
    fullname: Aleksic
– volume: 33
  start-page: 2780
  year: 2015
  ident: B79
  article-title: Talimogene laherparepvec improves durable response rate in patients with advanced melanoma
  publication-title: J Clin Oncol.
  doi: 10.1200/JCO.2014.58.3377
  contributor:
    fullname: Andtbacka
– volume: 25
  start-page: 2440
  year: 2017
  ident: B83
  article-title: Adenovirotherapy delivering cytokine and checkpoint inhibitor augments CAR T cells against metastatic head and neck cancer
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2017.09.010
  contributor:
    fullname: Rosewell Shaw
– volume: 20
  start-page: 652
  year: 2012
  ident: B53
  article-title: Long-term persistence of CD4(+) but rapid disappearance of CD8(+) T cells expressing an MHC class I-restricted TCR of nanomolar affinity
  publication-title: Mol Ther.
  doi: 10.1038/mt.2011.286
  contributor:
    fullname: Engels
– volume: 18
  start-page: 413
  year: 2010
  ident: B21
  article-title: Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication
  publication-title: Mol Ther.
  doi: 10.1038/mt.2009.210
  contributor:
    fullname: Zhong
– volume: 126
  start-page: 165
  year: 2009
  ident: B49
  article-title: T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity
  publication-title: Immunology
  doi: 10.1111/j.1365-2567.2008.03015.x
  contributor:
    fullname: Stone
– volume: 44
  start-page: 1444
  year: 2016
  ident: B54
  article-title: Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma
  publication-title: Immunity
  doi: 10.1016/j.immuni.2016.05.014
  contributor:
    fullname: Posey
– volume: 31
  start-page: 71
  year: 2013
  ident: B68
  article-title: Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.2459
  contributor:
    fullname: Kloss
– volume: 75
  start-page: 3596
  year: 2015
  ident: B37
  article-title: Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-15-0159
  contributor:
    fullname: Liu
– volume: 24
  start-page: 95
  year: 2018
  ident: B86
  article-title: Regional delivery of chimeric antigen receptor-engineered T cells effectively targets HER2(+) breast cancer metastasis to the brain
  publication-title: Clin Cancer Res.
  doi: 10.1158/1078-0432.CCR-17-2041
  contributor:
    fullname: Priceman
– volume: 5
  start-page: 3928
  year: 1999
  ident: B26
  article-title: Bypassing immunization: optimized design of “designer T cells” against carcinoembryonic antigen (CEA)-expressing tumors, and lack of suppression by soluble CEA
  publication-title: Clin Cancer Res.
  contributor:
    fullname: Nolan
– volume: 111
  start-page: 17576
  year: 2014
  ident: B7
  article-title: Molecular architecture of the alphabeta T cell receptor-CD3 complex
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1420936111
  contributor:
    fullname: Birnbaum
– volume: 126
  start-page: 3036
  year: 2016
  ident: B71
  article-title: Tandem CAR T cells targeting HER2 and IL13Ralpha2 mitigate tumor antigen escape
  publication-title: J Clin Invest.
  doi: 10.1172/JCI83416
  contributor:
    fullname: Hegde
– volume: 419
  start-page: 845
  year: 2002
  ident: B29
  article-title: Direct observation of ligand recognition by T cells
  publication-title: Nature
  doi: 10.1038/nature01076
  contributor:
    fullname: Irvine
– volume: 186
  start-page: 757
  year: 1997
  ident: B33
  article-title: Single cell analysis reveals regulated hierarchical T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4+ T cells
  publication-title: J Exp Med.
  doi: 10.1084/jem.186.5.757
  contributor:
    fullname: Itoh
– volume: 16
  start-page: 96
  year: 2006
  ident: B58
  article-title: Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance
  publication-title: Glycobiology
  doi: 10.1093/glycob/cwj044
  contributor:
    fullname: Sorensen
– volume: 2
  start-page: 112
  year: 2014
  ident: B100
  article-title: Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-13-0170
  contributor:
    fullname: Beatty
– volume: 18
  start-page: 676
  year: 2004
  ident: B13
  article-title: Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia
  publication-title: Leukemia
  doi: 10.1038/sj.leu.2403302
  contributor:
    fullname: Imai
– volume: 77
  start-page: 1296
  year: 2017
  ident: B85
  article-title: A multifunctional role for adjuvant anti-4-1BB therapy in augmenting antitumor response by chimeric antigen receptor T cells
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-16-1831
  contributor:
    fullname: Mardiana
– volume: 3
  start-page: 96976
  year: 2018
  ident: B14
  article-title: Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation
  publication-title: JCI Insight
  doi: 10.1172/jci.insight.96976
  contributor:
    fullname: Guedan
– volume: 126
  start-page: 4262
  year: 2016
  ident: B99
  article-title: Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia
  publication-title: J Clin Invest.
  doi: 10.1172/JCI84813
  contributor:
    fullname: Paszkiewicz
– volume: 22
  start-page: 487
  year: 2015
  ident: B77
  article-title: Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses
  publication-title: Cancer Gene Ther.
  doi: 10.1038/cgt.2015.47
  contributor:
    fullname: Kuramitsu
– volume: 108
  start-page: 9089
  year: 2011
  ident: B31
  article-title: T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clusters
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1018771108
  contributor:
    fullname: Manz
– volume: 111
  start-page: E3679
  year: 2014
  ident: B32
  article-title: A sharp T-cell antigen receptor signaling threshold for T-cell proliferation
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1413726111
  contributor:
    fullname: Au-Yeung
– volume: 7
  start-page: 34341
  year: 2016
  ident: B93
  article-title: Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.9114
  contributor:
    fullname: Suarez
– volume: 33
  start-page: 326
  year: 2010
  ident: B16
  article-title: Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation
  publication-title: Immunity
  doi: 10.1016/j.immuni.2010.09.006
  contributor:
    fullname: Yokosuka
– volume: 2
  start-page: e105
  year: 2013
  ident: B69
  article-title: TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy
  publication-title: Mol Ther Nucleic Acids
  doi: 10.1038/mtna.2013.32
  contributor:
    fullname: Grada
– volume: 24
  start-page: 106
  year: 2018
  ident: B78
  article-title: Lenalidomide enhances the function of CS1 chimeric antigen receptor-redirected T cells against multiple myeloma
  publication-title: Clin Cancer Res.
  doi: 10.1158/1078-0432.CCR-17-0344
  contributor:
    fullname: Wang
– volume: 375
  start-page: 148
  year: 1995
  ident: B48
  article-title: Serial triggering of many T-cell receptors by a few peptide-MHC complexes
  publication-title: Nature
  doi: 10.1038/375148a0
  contributor:
    fullname: Valitutti
– volume: 20
  start-page: 633
  year: 2012
  ident: B27
  article-title: Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor
  publication-title: Mol Ther.
  doi: 10.1038/mt.2011.256
  contributor:
    fullname: Lanitis
– volume: 21
  start-page: 2087
  year: 2013
  ident: B70
  article-title: Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma
  publication-title: Mol Ther.
  doi: 10.1038/mt.2013.185
  contributor:
    fullname: Hegde
– volume: 58
  start-page: 1116
  year: 1998
  ident: B25
  article-title: An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30
  publication-title: Cancer Res.
  contributor:
    fullname: Hombach
– volume: 194
  start-page: 911
  year: 2015
  ident: B34
  article-title: Target antigen density governs the efficacy of anti-CD20-CD28-CD3 zeta chimeric antigen receptor-modified effector CD8+ T cells
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.1402346
  contributor:
    fullname: Watanabe
– volume: 50
  start-page: 39
  year: 2011
  ident: B50
  article-title: T cell recognition of weak ligands: roles of signaling, receptor number, and affinity
  publication-title: Immunol Res.
  doi: 10.1007/s12026-011-8204-3
  contributor:
    fullname: Edwards
– volume: 6
  start-page: 36
  year: 2018
  ident: B51
  article-title: High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-17-0211
  contributor:
    fullname: Richman
– volume: 20
  start-page: 3025
  year: 2017
  ident: B91
  article-title: Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2017.09.002
  contributor:
    fullname: Hu
– volume: 15
  start-page: 751
  year: 2001
  ident: B17
  article-title: The immunological synapse of CTL contains a secretory domain and membrane bridges
  publication-title: Immunity
  doi: 10.1016/S1074-7613(01)00234-5
  contributor:
    fullname: Stinchcombe
– volume: 18
  start-page: 843
  year: 2010
  ident: B4
  article-title: Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2
  publication-title: Mol Ther.
  doi: 10.1038/mt.2010.24
  contributor:
    fullname: Morgan
– volume: 33
  start-page: 540
  year: 2015
  ident: B3
  article-title: Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor
  publication-title: J Clin Oncol.
  doi: 10.1200/JCO.2014.56.2025
  contributor:
    fullname: Kochenderfer
– volume: 25
  start-page: 1946
  year: 2017
  ident: B61
  article-title: A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2017.04.024
  contributor:
    fullname: Drent
– volume: 5
  start-page: 1152
  year: 2017
  ident: B88
  article-title: Safety and efficacy of intratumoral injections of Chimeric Antigen Receptor (CAR) T cells in metastatic breast cancer
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-17-0189
  contributor:
    fullname: Tchou
– volume: 21
  start-page: 17
  year: 2017
  ident: B66
  article-title: Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell survival and is vector-dependent
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2017.09.015
  contributor:
    fullname: Gomes-Silva
– volume: 173
  start-page: 7647
  year: 2004
  ident: B62
  article-title: T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.173.12.7647
  contributor:
    fullname: Chmielewski
– volume: 1
  start-page: 863
  year: 2012
  ident: B35
  article-title: A sensitivity scale for targeting T cells with chimeric antigen receptors (CARs) and bispecific T-cell Engagers (BiTEs)
  publication-title: Oncoimmunology
  doi: 10.4161/onci.20592
  contributor:
    fullname: Stone
– volume: 176
  start-page: 7308
  year: 2006
  ident: B42
  article-title: Quantifying and imaging NY-ESO-1/LAGE-1-derived epitopes on tumor cells using high affinity T cell receptors
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.176.12.7308
  contributor:
    fullname: Purbhoo
– volume: 19
  start-page: 620
  year: 2011
  ident: B6
  article-title: T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis
  publication-title: Mol Ther.
  doi: 10.1038/mt.2010.272
  contributor:
    fullname: Parkhurst
– volume: 36
  start-page: 346
  year: 2018
  ident: B92
  article-title: IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.4086
  contributor:
    fullname: Adachi
– volume: 25
  start-page: 165
  year: 2018
  ident: B57
  article-title: Driving cars to the clinic for solid tumors
  publication-title: Gene Ther.
  doi: 10.1038/s41434-018-0007-x
  contributor:
    fullname: Castellarin
– volume: 3
  start-page: 483
  year: 2015
  ident: B40
  article-title: CAR-T cells inflict sequential killing of multiple tumor target cells
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-15-0048
  contributor:
    fullname: Davenport
– volume: 23
  start-page: 1436
  year: 2017
  ident: B55
  article-title: The activated conformation of integrin beta7 is a novel multiple myeloma-specific target for CAR T cell therapy
  publication-title: Nat Med.
  doi: 10.1038/nm.4431
  contributor:
    fullname: Hosen
– volume: 21
  start-page: 4062
  year: 2015
  ident: B15
  article-title: Bioactivity and safety of IL13Ralpha2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma
  publication-title: Clin Cancer Res.
  doi: 10.1158/1078-0432.CCR-15-0428
  contributor:
    fullname: Brown
– volume: 25
  start-page: 274
  year: 2017
  ident: B89
  article-title: Masked chimeric antigen receptor for tumor-specific activation
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2016.10.011
  contributor:
    fullname: Han
– volume: 113
  start-page: 4885
  year: 2009
  ident: B96
  article-title: Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance
  publication-title: Blood
  doi: 10.1182/blood-2008-08-175208
  contributor:
    fullname: Hiraga
– volume: 281
  start-page: 572
  year: 1998
  ident: B9
  article-title: Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation
  publication-title: Science
  doi: 10.1126/science.281.5376.572
  contributor:
    fullname: Kersh
– volume: 18
  start-page: 6436
  year: 2012
  ident: B73
  article-title: Redirecting gene-modified T cells toward various cancer types using tagged antibodies
  publication-title: Clin Cancer Res.
  doi: 10.1158/1078-0432.CCR-12-1449
  contributor:
    fullname: Tamada
– volume: 75
  start-page: 3505
  year: 2015
  ident: B60
  article-title: Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-15-0139
  contributor:
    fullname: Caruso
– volume: 74
  start-page: 5195
  year: 2014
  ident: B82
  article-title: Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-14-0697
  contributor:
    fullname: Nishio
– volume: 24
  start-page: e20
  year: 2006
  ident: B5
  article-title: Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience
  publication-title: J Clin Oncol.
  doi: 10.1200/JCO.2006.05.9964
  contributor:
    fullname: Lamers
– volume: 19
  start-page: 3153
  year: 2013
  ident: B75
  article-title: Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells
  publication-title: Clin Cancer Res.
  doi: 10.1158/1078-0432.CCR-13-0330
  contributor:
    fullname: Hudecek
– volume: 39
  start-page: 846
  year: 2013
  ident: B30
  article-title: A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells
  publication-title: Immunity
  doi: 10.1016/j.immuni.2013.08.036
  contributor:
    fullname: Huang
– volume: 5
  start-page: 1282
  year: 2015
  ident: B94
  article-title: Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-15-1020
  contributor:
    fullname: Sotillo
– volume: 64
  start-page: 7985
  year: 2004
  ident: B95
  article-title: Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-04-1525
  contributor:
    fullname: Garnett
– volume: 164
  start-page: 780
  year: 2016
  ident: B102
  article-title: Engineering customized cell sensing and response behaviors using synthetic notch receptors
  publication-title: Cell
  doi: 10.1016/j.cell.2016.01.012
  contributor:
    fullname: Morsut
– volume: 167
  start-page: 419
  year: 2016
  ident: B103
  article-title: Engineering T cells with customized therapeutic response programs using synthetic notch receptors
  publication-title: Cell
  doi: 10.1016/j.cell.2016.09.011
  contributor:
    fullname: Roybal
– volume: 31
  start-page: 999
  year: 2013
  ident: B59
  article-title: Reassessing target antigens for adoptive T-cell therapy
  publication-title: Nat Biotechnol.
  doi: 10.1038/nbt.2725
  contributor:
    fullname: Hinrichs
– volume: 368
  start-page: 1509
  year: 2013
  ident: B1
  article-title: Chimeric antigen receptor-modified T cells for acute lymphoid leukemia
  publication-title: N Engl J Med.
  doi: 10.1056/NEJMoa1215134
  contributor:
    fullname: Grupp
– volume: 26
  start-page: 963
  year: 2018
  ident: B22
  article-title: Immunological synapse predicts effectiveness of chimeric antigen receptor cells
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2018.01.020
  contributor:
    fullname: Xiong
– volume: 185
  start-page: 6545
  year: 2010
  ident: B52
  article-title: Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.1001867
  contributor:
    fullname: Caserta
– volume: 24
  start-page: 1160
  year: 2010
  ident: B97
  article-title: Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety
  publication-title: Leukemia
  doi: 10.1038/leu.2010.75
  contributor:
    fullname: Hoyos
– volume: 377
  start-page: 32
  year: 1995
  ident: B8
  article-title: Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor
  publication-title: Nature
  doi: 10.1038/377032a0
  contributor:
    fullname: Hatada
– volume: 184
  start-page: 4936
  year: 2010
  ident: B46
  article-title: Evidence for a TCR affinity threshold delimiting maximal CD8 T cell function
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.1000173
  contributor:
    fullname: Schmid
– volume: 375
  start-page: 2561
  year: 2016
  ident: B87
  article-title: Regression of glioblastoma after chimeric antigen receptor T-cell therapy
  publication-title: N Engl J Med.
  doi: 10.1056/NEJMoa1610497
  contributor:
    fullname: Brown
– volume: 365
  start-page: 1673
  year: 2011
  ident: B98
  article-title: Inducible apoptosis as a safety switch for adoptive cell therapy
  publication-title: N Engl J Med.
  doi: 10.1056/NEJMoa1106152
  contributor:
    fullname: Di Stasi
– volume: 3
  start-page: 356
  year: 2015
  ident: B65
  article-title: Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-14-0186
  contributor:
    fullname: Frigault
– volume: 30
  start-page: 684
  year: 2007
  ident: B63
  article-title: Redirected activity of human antitumor chimeric immune receptors is governed by antigen and receptor expression levels and affinity of interaction
  publication-title: J Immunother.
  doi: 10.1097/CJI.0b013e3180de5d90
  contributor:
    fullname: Turatti
– volume: 6
  start-page: 605
  year: 2018
  ident: B84
  article-title: Improving CART-cell therapy of solid tumors with oncolytic virus-driven production of a bispecific T-cell engager
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-17-0314
  contributor:
    fullname: Wing
– volume: 371
  start-page: 1507
  year: 2014
  ident: B2
  article-title: Chimeric antigen receptor T cells for sustained remissions in leukemia
  publication-title: N Engl J Med.
  doi: 10.1056/NEJMoa1407222
  contributor:
    fullname: Maude
– volume: 180
  start-page: 4901
  year: 2008
  ident: B74
  article-title: Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.180.7.4901
  contributor:
    fullname: Wilkie
– volume: 3
  start-page: 99573
  year: 2018
  ident: B81
  article-title: Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses
  publication-title: JCI Insight
  doi: 10.1172/jci.insight.99573
  contributor:
    fullname: Watanabe
– volume: 543
  start-page: 113
  year: 2017
  ident: B41
  article-title: Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
  publication-title: Nature
  doi: 10.1038/nature21405
  contributor:
    fullname: Eyquem
– volume: 177
  start-page: 6548
  year: 2006
  ident: B45
  article-title: Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.177.9.6548
  contributor:
    fullname: Johnson
– volume: 161
  start-page: 2791
  year: 1998
  ident: B12
  article-title: Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product
  publication-title: J Immunol.
  doi: 10.4049/jimmunol.161.6.2791
  contributor:
    fullname: Finney
– volume: 9
  start-page: eaaa0984
  year: 2017
  ident: B56
  article-title: A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma
  publication-title: Sci Transl Med.
  doi: 10.1126/scitranslmed.aaa0984
  contributor:
    fullname: O'Rourke
– volume: 119
  start-page: 4133
  year: 2012
  ident: B90
  article-title: Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning
  publication-title: Blood
  doi: 10.1182/blood-2011-12-400044
  contributor:
    fullname: Pegram
– volume: 115
  start-page: E2068
  year: 2018
  ident: B23
  article-title: Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1716266115
  contributor:
    fullname: Davenport
– volume: 110
  start-page: 6488
  year: 2013
  ident: B39
  article-title: Imaging burst kinetics and spatial coordination during serial killing by single natural killer cells
  publication-title: Proc Natl Acad Sci USA.
  doi: 10.1073/pnas.1221312110
  contributor:
    fullname: Choi
– volume: 4
  start-page: 658
  year: 2016
  ident: B101
  article-title: A tet-on inducible system for controlling CD19-chimeric antigen receptor expression upon drug administration
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-16-0043
  contributor:
    fullname: Sakemura
– volume: 25
  start-page: 2189
  year: 2017
  ident: B36
  article-title: Tumor antigen and receptor densities regulate efficacy of a chimeric antigen receptor targeting anaplastic lymphoma kinase
  publication-title: Mol Ther.
  doi: 10.1016/j.ymthe.2017.06.008
  contributor:
    fullname: Walker
– volume: 7
  start-page: 14366
  year: 2017
  ident: B64
  article-title: Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity
  publication-title: Sci Rep.
  doi: 10.1038/s41598-017-14749-3
  contributor:
    fullname: Park
– volume: 32
  start-page: 1059
  year: 2012
  ident: B67
  article-title: Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling
  publication-title: J Clin Immunol.
  doi: 10.1007/s10875-012-9689-9
  contributor:
    fullname: Wilkie
– volume: 168
  start-page: 724
  year: 2017
  ident: B10
  article-title: The principles of engineering immune cells to treat cancer
  publication-title: Cell
  doi: 10.1016/j.cell.2017.01.016
  contributor:
    fullname: Lim
– volume: 14
  start-page: 317
  year: 2018
  ident: B28
  article-title: Rewiring T-cell responses to soluble factors with chimeric antigen receptors
  publication-title: Nat Chem Biol.
  doi: 10.1038/nchembio.2565
  contributor:
    fullname: Chang
– volume: 72
  start-page: 1844
  year: 2012
  ident: B72
  article-title: A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-11-3890
  contributor:
    fullname: Urbanska
– volume: 443
  start-page: 462
  year: 2006
  ident: B18
  article-title: Centrosome polarization delivers secretory granules to the immunological synapse
  publication-title: Nature
  doi: 10.1038/nature05071
  contributor:
    fullname: Stinchcombe
– volume: 122
  start-page: 863
  year: 2013
  ident: B43
  article-title: Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma
  publication-title: Blood
  doi: 10.1182/blood-2013-03-490565
  contributor:
    fullname: Linette
– volume: 3
  start-page: 125
  year: 2015
  ident: B76
  article-title: The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity
  publication-title: Cancer Immunol Res.
  doi: 10.1158/2326-6066.CIR-14-0127
  contributor:
    fullname: Hudecek
– volume: 14
  start-page: 559
  year: 2014
  ident: B80
  article-title: Going viral with cancer immunotherapy
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc3770
  contributor:
    fullname: Lichty
– volume: 10
  start-page: e0144787
  year: 2015
  ident: B20
  article-title: Evaluation of intracellular signaling downstream chimeric antigen receptors
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0144787
  contributor:
    fullname: Karlsson
SSID ssj0000493335
Score 2.6038187
SecondaryResourceType review_article
Snippet A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
StartPage 2486
SubjectTerms Animals
Antigens, Neoplasm - immunology
cancer immunology
chimeric antigen receptors
Humans
immune synapse formation
Immunological Synapses - metabolism
Immunology
immunotherapy
Immunotherapy, Adoptive - methods
Neoplasms - immunology
Neoplasms - therapy
Receptors, Antigen, T-Cell - genetics
T cell biology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LT-MwELYQEhKX1fJYtrxkJC4cAsGvxNygaoWQ4ACtlpvlxI620CaItjz-PTNxgBatxGWPSZzYmZlkvk-2vyFkH1KAYDlLI5ckNoKg0JGWjmE1d-GA4yapxd3Il1fqvC8ubuXtTKkvXBMW5IGD4Y48pBxfxIlXHrW00gwYBGQ9lnqc4MkCW4_1DJm6C7iXcy7DvCSwMH1UDEajKS7lSg9RxkvN5aFarv9fGPPrUsmZ3NP9SX40oJGehsGukAVfrpKlUEbydY08dV4ewu4UCnCO9j63VNE_QLmrZwrIlLZPr2mPtv1w2LR4pYOS3lTDgaO96ah6HJ_gBYqFsMsxhQfSfnkfDqpi9vam43XS73Z67fOoqacQ5QALJpF2ykphFecWnGC1ZJrZwsscSFaeAm8TwgkghFIJ73hsVWbhh6BdbrnUtkj4L7JYVqX_TSjYH5AKL44zxgGCcO0yFysnlEeJPGlb5ODduuYhyGYYoBvoCVN7wqAnTO2JFjlD83-0Q8Hr-gSEgWnCwHwXBi2y9-48Ax8IznrY0lfTsWHItzW8yHGLbARnfnTFY8CjMoYhJHNunhvL_JVy8LcW4VaQ84Hdbf6PwW-RZTQHpkSmtsni5HHqdwDrTLLdOqzfAJUw-FA
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Scholars Portal Open Access Journals
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LT9wwELYoCKkXBJSWbQEZqRcOgaxfiZEQghUIIdFD2RXcLCd2YNvdBPYB7L9nJgmPRXvgmNjxa8aZ75M9M4T8BhMgWMriwEWRDUApdKClY5jNXTjguFFs0Rv54o8664jza3n95h5dL-BwJrXDfFKdQW_36X5yCBv-ABkn2Nu9rNvvj_GWVryLEbrUF7LAMCwXXuSrwf6_CgtzXmbcbColAtBkUZ1bzmxkyk6V4fxnYdCPVynf2abTZbJUg0p6VGnBCpnz-SpZrNJMTr6Rh5Onu8p7hQLco-03lyt6BZS8eKSAXGnr6C9t05bv9eoaE9rN6WXR6zraHveLwXAfCygmys6HFBqknfx_9VBk7z-vO14jndOTdussqPMtBCnAhlGgnbJSWMW5BSFZLZlmNvMyBRKWxsDrhHACCKNUwjseWpVY-GFol1outc0i_p3M50Xu1wnlLAYkw7NmwjhAFK5d4kLlhPIYQk_aBtl5WV1zV4XVMEBHUBKmlIRBSZhSEg1yjMv_Wg8DYpcvisGNqfeX8YBMfBZGXnkMuRYnQDQBHLHY4zlgEjbI9ovwDGwgPBWxuS_GQ8OQj2uYSLNBflTCfO2Kh4BXZQhDiKbEPDWW6ZK8e1sG6VaACYD9_fxEv7_IV5wtWkSmNsj8aDD2mwB1RslWqcHPns34yg
  priority: 102
  providerName: Scholars Portal
Title Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology
URI https://www.ncbi.nlm.nih.gov/pubmed/30416506
https://www.proquest.com/docview/2132290701
https://pubmed.ncbi.nlm.nih.gov/PMC6212550
https://doaj.org/article/e240ef07e6e44518b60174328e1690b0
Volume 9
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Jj9MwFLZmRkLigtgJy8hIXDiki7fE3IZqhhFSEYJW9GY5sTMEGqfqAsy_570sQ4s4cYmUOIkdfy_x98XP7xHyCoYAwXKWxi5JbAxGoWMtHcNs7sKBxk1Si6uRpx_U5Vy8X8jFEZH9WpjGaT_PykFYVoNQfm18K1dVPuz9xIYfpxMF31sMr31MjsFA9yT6t5bycs5lOyUJAkwPi7KqdujFlQ4wghdmLQIRPwZuog5GoyZo_7-Y5t8Ok3sj0MVdcqejjvSsbeI9cuTDfXKrTSZ5_YD8OP-1ateoUCB1dPZnYRX9AsK7_kmBn9LJ2Sc6oxO_XHZnXNMy0M_1snR0tqvq9eYNFlBMhx02FG5I5-F7u1MX-5d3FT8k84vz2eQy7rIqxDmQg22snbJSWMW5BSislkwzW3iZg9TKU1BvQjgBslAq4R0fWZVZ-Cxol1sutS0S_oichDr4J4RylgJf4cU4YxyICNcucyPlhPIYKE_aiLzue9es2uAZBkQHgmIaUAyCYhpQIvIWu__mPAx73Ryo11emA9944B--GCVeeQyslmYgJ4ECsdTjbF82isjLHjwDrwnOfdjg693GMFTdGh5kHJHHLZg3VfXGEJHkAOaDthyWgGU2obg7S3z631c-I7exD3A0ZOo5Odmud_4F0Jxtdtr8HoDtu8UYtlORnjaG_hu3L_za
link.rule.ids 230,315,730,783,787,867,888,2109,24332,27938,27939,53806,53808
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lc9MwEN4pZRi48H6Yp5jhwsGJI1myxa1k2gnQdBhwoDePbMnUbWxnkhgov56VHyXpcIGjLcuvXUnfN9r9FuAVLgE-TWno6iBQLjqFdCXX1FZz9zVy3CBUNht5eiQmM__9MT_eAd7nwjRB-2mSD8p5MSjzkya2clGkwz5ObPhxOhY431p57StwFcerJzZI-mkLehljvN2URAomh1leFLWN4woHVsPL1i1CGj9CdCK21qNGtv9vWPNyyOTGGnRwC770b9-GnpwN6nUySH9dEnb858-7DTc7VEr22uY7sGPKu3CtrVN5fg--7_9ctOkvBPEiif7kbJGvyOmrHwShLxnvfSIRGZv5vLvinOQl-VzNc02iuqiWqze2gdhK2-WK4A3JrDxrD6pss3v34PswO9iPxhO3K9jgpog71q7UQnFfCcYUWllJTiVVmeEpsrg0RGLo-9pHxsmFbzTzlEgUzjhSp4pxqbKAPYDdsirNIyCMhgiFWDZKKEOMw6ROtCe0L4zV4OPKgde92eJFq8sRI5-x1o4ba8fW2nFjbQfeWrteXGcVtZsT1fJb3P342CC0MZkXGGGsZluYIFNFdEVDYzcSE8-Bl71XxDgC7baKKk1Vr2JqCb3EDxk58LD1kotH9V7mQLDlP1vvst2CXtGofHde8Pi_e76A65Noehgfvjv68ARu2P9hF10qnsLuelmbZ4im1snzZuz8BuH2HBY
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagCNRLeZeUl5G4cEg2aydOzK0sXZVHqwp2RcXFcmIHQjfJancDlF_PTB5lt-LUY2I7iT3j-Pvk8TeEvIQlIGApi10TRdoFp5CuDA3DbO6BAY4bxRpPIx8di8Np8P40PF1L9dUE7adJ7pWzwivz701s5bxIB32c2ODkaCTgf4vy2nOTDa6TGzBn_XiNqP9ogS_nPGw3JoGGyUGWF0WNsVyxhzpemLsIqPwQEIrYWJMa6f7_4c3LYZNr69D4Nvna96ANPznz6lXipX8uiTteqYt3yE6HTul-W-UuuWbLe-Rmm6_y_D75efB73h6DoYAb6eTf2S36Bbh99YsCBKaj_U90Qkd2NutqnNO8pJ-rWW7opC6qxfI1FlDMuF0uKTyQTsuz9qLK1pt3L35ApuODyejQ7RI3uCngj5UrjdBhoAXnGqytZcgk05kNU2BzaQwEMQhMAMwzFIE13Nci0fDnkSbVPJQ6i_hDslVWpX1EKGcxQCKeDRPGAetwaRLjCxMIi1p8oXbIq950at7qcyjgNWhx1VhcocVVY3GHvEHbXtRDZe3mRrX4prrBVxYgjs38yAqL2m1xAowVUBaLLW4oJr5DXvSeoWAm4vaKLm1VLxVDYi-hI0OH7LaecvGq3tMcEm340Ma3bJaAZzRq350n7F255XNy6-TtWH18d_zhMdnG4cC1l4knZGu1qO1TAFWr5Fkzff4C2u8elg
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Expanding+the+Therapeutic+Window+for+CAR+T+Cell+Therapy+in+Solid+Tumors%3A+The+Knowns+and+Unknowns+of+CAR+T+Cell+Biology&rft.jtitle=Frontiers+in+immunology&rft.au=Watanabe%2C+Keisuke&rft.au=Kuramitsu%2C+Shunichiro&rft.au=Posey%2C+Avery+D&rft.au=June%2C+Carl+H&rft.date=2018-10-26&rft.issn=1664-3224&rft.eissn=1664-3224&rft.volume=9&rft.spage=2486&rft_id=info:doi/10.3389%2Ffimmu.2018.02486&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1664-3224&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1664-3224&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1664-3224&client=summon