Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine
With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic cell (DC) vaccines in combination with T cell-targeting immunotherapies to potentially maximize the therapeutic impact of DC vaccines. Here, w...
Saved in:
Published in | Vaccines (Basel) Vol. 8; no. 1; p. 25 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI
14.01.2020
MDPI AG |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic cell (DC) vaccines in combination with T cell-targeting immunotherapies to potentially maximize the therapeutic impact of DC vaccines. Here, we describe the development and optimization of a Good Manufacturing Practice (GMP)-compliant manufacturing process based on tumor lysate as a tumor antigen source for the production of an oxidized tumor cell lysate loaded DC (OC-DC) vaccine. The manufacturing process required one day for lysate preparation and six days for OC-DC vaccine production. Tumor lysate production was standardized based on an optimal tumor digestion protocol and the immunogenicity was improved through oxidation using hypochloric acid prior to freeze-thaw cycles resulting in the oxidized tumor cell lysate (OC-L). Next, monocytes were selected using the CliniMACS prodigy closed system and were placed in culture in cell factories in the presence of IL-4 and GM-CSF. Immature DCs were loaded with OC-L and matured using MPLA-IFNγ. After assessing the functionality of the OC-DC cells (IL12p70 secretion and COSTIM assay), the OC-DC vaccine was cryopreserved in multiple doses for single use. Finally, the stability of the formulated doses was tested and validated. We believe this GMP-compliant DC vaccine manufacturing process will facilitate access of patients to personalized DC vaccines, and allow for multi-center clinical trials. |
---|---|
AbstractList | With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic cell (DC) vaccines in combination with T cell-targeting immunotherapies to potentially maximize the therapeutic impact of DC vaccines. Here, we describe the development and optimization of a Good Manufacturing Practice (GMP)-compliant manufacturing process based on tumor lysate as a tumor antigen source for the production of an oxidized tumor cell lysate loaded DC (OC-DC) vaccine. The manufacturing process required one day for lysate preparation and six days for OC-DC vaccine production. Tumor lysate production was standardized based on an optimal tumor digestion protocol and the immunogenicity was improved through oxidation using hypochloric acid prior to freeze-thaw cycles resulting in the oxidized tumor cell lysate (OC-L). Next, monocytes were selected using the CliniMACS prodigy closed system and were placed in culture in cell factories in the presence of IL-4 and GM-CSF. Immature DCs were loaded with OC-L and matured using MPLA-IFNγ. After assessing the functionality of the OC-DC cells (IL12p70 secretion and COSTIM assay), the OC-DC vaccine was cryopreserved in multiple doses for single use. Finally, the stability of the formulated doses was tested and validated. We believe this GMP-compliant DC vaccine manufacturing process will facilitate access of patients to personalized DC vaccines, and allow for multi-center clinical trials. |
Author | Dutoit, Laeticia Danilo, Maxime Kandalaft, Lana E Gannon, Philippe O Harari, Alexandre Lingre, Emilie Boudousquié, Caroline Balint, Klara Boand, Valérie |
AuthorAffiliation | 2 Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Maxime.Danilo@chuv.ch 1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; valerie.boand@gmail.com (V.B.); Emilie.Lingre@chuv.ch (E.L.); Laeticia.Dutoit@chuv.ch (L.D.); Klara.Balint@chuv.ch (K.B.); Alexandre.Harari@chuv.ch (A.H.); Philippe.Gannon@chuv.ch (P.O.G.) |
AuthorAffiliation_xml | – name: 1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; valerie.boand@gmail.com (V.B.); Emilie.Lingre@chuv.ch (E.L.); Laeticia.Dutoit@chuv.ch (L.D.); Klara.Balint@chuv.ch (K.B.); Alexandre.Harari@chuv.ch (A.H.); Philippe.Gannon@chuv.ch (P.O.G.) – name: 2 Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Maxime.Danilo@chuv.ch |
Author_xml | – sequence: 1 givenname: Caroline surname: Boudousquié fullname: Boudousquié, Caroline organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 2 givenname: Valérie surname: Boand fullname: Boand, Valérie organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 3 givenname: Emilie surname: Lingre fullname: Lingre, Emilie organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 4 givenname: Laeticia surname: Dutoit fullname: Dutoit, Laeticia organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 5 givenname: Klara surname: Balint fullname: Balint, Klara organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 6 givenname: Maxime surname: Danilo fullname: Danilo, Maxime organization: Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland – sequence: 7 givenname: Alexandre surname: Harari fullname: Harari, Alexandre organization: Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland – sequence: 8 givenname: Philippe O surname: Gannon fullname: Gannon, Philippe O organization: Department of Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland – sequence: 9 givenname: Lana E surname: Kandalaft fullname: Kandalaft, Lana E organization: Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31947581$$D View this record in MEDLINE/PubMed |
BookMark | eNpdksFvFCEUxiemxtbaszfD0ctaGGZguJiYba1NtukeqvFG3sBjpZmBFWY2aeMfL7q1aeUCeXzvx8d773V1EGLAqnrL6AfOFT3dgTE-YO4oo7RuX1RHNZViwRX_fvDkfFid5HxLy1KMd0K-qg45U41sO3ZU_TrDHQ5xO2KYCARLrreTH_09TD4GEh0BcnG1XizjuB08FM0VhNmBmebkw4asUzSYM3ExFeUaU44BBn-PltzMYwmu7jJMSM4w2OQnb8gSh4F82zt_U710MGQ8ediPq6-fz2-WXxar64vL5afVwjStmhY1tzVKsMpyy5wVjnNwom9p01tqWC_RdLVEW_7HqOioYMpRpqwTvKsZSn5cXe65NsKt3iY_QrrTEbz-G4hpoyEVcwNqIbva9UAd9H1jpOidMkKZlkvZNdZAYX3cs7ZzP6I1pW4JhmfQ5zfB_9CbuNOStbJpWAG8fwCk-HPGPOnRZ1OqAgHjnHXNGyaYVHVXpKd7qUkx54Tu8RlG9Z8R0P-NQMl499Tdo_5fw_lviuCzEA |
CitedBy_id | crossref_primary_10_1016_j_trecan_2023_02_004 crossref_primary_10_1007_s12032_023_02220_5 crossref_primary_10_1186_s12865_023_00552_5 crossref_primary_10_2217_nnm_2020_0032 crossref_primary_10_1016_j_omtm_2024_101250 crossref_primary_10_1136_jitc_2021_003190 crossref_primary_10_1007_s10404_022_02568_6 crossref_primary_10_3390_vaccines12020112 crossref_primary_10_1159_000512451 crossref_primary_10_1016_j_bioactmat_2021_03_003 crossref_primary_10_1002_advs_202300121 crossref_primary_10_3390_ijms222212339 |
Cites_doi | 10.1016/j.coi.2015.12.001 10.1056/NEJMoa1001294 10.1016/j.jcyt.2018.06.006 10.1371/journal.pone.0052301 10.1097/CJI.0b013e3180ca7cd6 10.1016/j.coi.2016.04.005 10.1016/j.jcyt.2014.02.017 10.21037/atm.2016.06.17 10.1111/j.1582-4934.2008.00304.x 10.1111/j.1365-2567.2004.02076.x 10.1186/1471-2164-15-190 10.1186/s12967-019-02133-w 10.1038/s41551-018-0250-x 10.1126/scitranslmed.aao5931 10.3389/fimmu.2019.01832 10.1038/nature22991 10.1007/s00262-010-0843-z 10.1016/j.jpba.2004.05.025 10.1097/CJI.0b013e3181cc266b 10.1158/1078-0432.CCR-15-1509 10.1016/j.jim.2003.12.008 10.4161/onci.22664 10.1186/1479-5876-9-198 10.1158/1078-0432.CCR-13-1185 10.1016/j.jim.2018.09.012 10.1016/j.vaccine.2007.07.031 10.1038/nature23003 10.4161/21624011.2014.963424 |
ContentType | Journal Article |
Copyright | 2020 by the authors. 2020 |
Copyright_xml | – notice: 2020 by the authors. 2020 |
DBID | NPM AAYXX CITATION 7X8 5PM DOA |
DOI | 10.3390/vaccines8010025 |
DatabaseName | PubMed CrossRef MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
DatabaseTitle | PubMed CrossRef MEDLINE - Academic |
DatabaseTitleList | CrossRef PubMed |
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 |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 2076-393X |
ExternalDocumentID | oai_doaj_org_article_6782fba0fabb4c76bf9c69c537784dca 10_3390_vaccines8010025 31947581 |
Genre | Journal Article |
GroupedDBID | 3V. 53G 5VS 8FE 8FH 8G5 AADQD AAHBH ABUWG ADBBV AFKRA AFZYC ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BBNVY BCNDV BENPR BHPHI BPHCQ CCPQU DIK DWQXO GNUQQ GROUPED_DOAJ GUQSH HCIFZ HYE IAO KQ8 LK8 M2O M48 M7P MODMG M~E NPM OK1 PGMZT PIMPY PQQKQ PROAC RIG RNS RPM AAYXX CITATION 7X8 5PM |
ID | FETCH-LOGICAL-c459t-23d2e7ad9d3d1fd6f33af6b504bd0c1b7ec827ed09110680619f019df63821e73 |
IEDL.DBID | RPM |
ISSN | 2076-393X |
IngestDate | Fri Oct 04 13:05:12 EDT 2024 Tue Sep 17 21:11:28 EDT 2024 Fri Aug 16 01:34:08 EDT 2024 Fri Aug 23 04:50:22 EDT 2024 Sat Sep 28 08:27:48 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 1 |
Keywords | tumor lysate manufacturing vaccine GMP dendritic cell immunotherapy |
Language | English |
License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c459t-23d2e7ad9d3d1fd6f33af6b504bd0c1b7ec827ed09110680619f019df63821e73 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ORCID | 0000-0003-3263-3999 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157441/ |
PMID | 31947581 |
PQID | 2341617928 |
PQPubID | 23479 |
ParticipantIDs | doaj_primary_oai_doaj_org_article_6782fba0fabb4c76bf9c69c537784dca pubmedcentral_primary_oai_pubmedcentral_nih_gov_7157441 proquest_miscellaneous_2341617928 crossref_primary_10_3390_vaccines8010025 pubmed_primary_31947581 |
PublicationCentury | 2000 |
PublicationDate | 20200114 |
PublicationDateYYYYMMDD | 2020-01-14 |
PublicationDate_xml | – month: 1 year: 2020 text: 20200114 day: 14 |
PublicationDecade | 2020 |
PublicationPlace | Switzerland |
PublicationPlace_xml | – name: Switzerland |
PublicationTitle | Vaccines (Basel) |
PublicationTitleAlternate | Vaccines (Basel) |
PublicationYear | 2020 |
Publisher | MDPI MDPI AG |
Publisher_xml | – name: MDPI – name: MDPI AG |
References | Shankar (ref_18) 2004; 36 Vormehr (ref_9) 2016; 39 Sarivalasis (ref_27) 2019; 17 ref_13 Chiang (ref_11) 2013; 19 ref_10 Saxena (ref_2) 2018; 2 Kandalaft (ref_26) 2013; 2 Bloy (ref_1) 2014; 3 Kantoff (ref_3) 2010; 363 Eyrich (ref_19) 2014; 16 Sahin (ref_5) 2017; 547 Elkord (ref_24) 2005; 114 Tureci (ref_6) 2016; 22 Bobisse (ref_8) 2016; 4 Dohnal (ref_22) 2009; 13 Karsten (ref_15) 2007; 25 Digklia (ref_28) 2019; 10 Visser (ref_16) 2010; 59 Coukos (ref_7) 2016; 41 ref_20 Chiang (ref_12) 2011; 9 Erdmann (ref_23) 2007; 30 Brabants (ref_14) 2018; 20 Rouas (ref_25) 2010; 33 Shankar (ref_17) 2004; 285 Ott (ref_4) 2017; 547 Erdmann (ref_21) 2018; 463 |
References_xml | – volume: 39 start-page: 14 year: 2016 ident: ref_9 article-title: Mutanome directed cancer immunotherapy publication-title: Curr. Opin. Immunol. doi: 10.1016/j.coi.2015.12.001 contributor: fullname: Vormehr – volume: 363 start-page: 411 year: 2010 ident: ref_3 article-title: Sipuleucel-T immunotherapy for castration-resistant prostate cancer publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1001294 contributor: fullname: Kantoff – volume: 20 start-page: 1164 year: 2018 ident: ref_14 article-title: An accelerated, clinical-grade protocol to generate high yields of type 1-polarizing messenger RNA-loaded dendritic cells for cancer vaccination publication-title: Cytotherapy doi: 10.1016/j.jcyt.2018.06.006 contributor: fullname: Brabants – ident: ref_20 doi: 10.1371/journal.pone.0052301 – volume: 30 start-page: 663 year: 2007 ident: ref_23 article-title: Effective clinical-scale production of dendritic cell vaccines by monocyte elutriation directly in medium, subsequent culture in bags and final antigen loading using peptides or RNA transfection publication-title: J. Immunother. doi: 10.1097/CJI.0b013e3180ca7cd6 contributor: fullname: Erdmann – volume: 41 start-page: 9 year: 2016 ident: ref_7 article-title: Mass spectrometry-based antigen discovery for cancer immunotherapy publication-title: Curr. Opin. Immunol. doi: 10.1016/j.coi.2016.04.005 contributor: fullname: Coukos – volume: 16 start-page: 946 year: 2014 ident: ref_19 article-title: Development and validation of a fully GMP-compliant production process of autologous, tumor-lysate-pulsed dendritic cells publication-title: Cytotherapy doi: 10.1016/j.jcyt.2014.02.017 contributor: fullname: Eyrich – volume: 4 start-page: 262 year: 2016 ident: ref_8 article-title: Neoantigen-based cancer immunotherapy publication-title: Ann. Transl. Med. doi: 10.21037/atm.2016.06.17 contributor: fullname: Bobisse – volume: 13 start-page: 125 year: 2009 ident: ref_22 article-title: Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines publication-title: J. Cell Mol. Med. doi: 10.1111/j.1582-4934.2008.00304.x contributor: fullname: Dohnal – volume: 114 start-page: 204 year: 2005 ident: ref_24 article-title: Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells publication-title: Immunology doi: 10.1111/j.1365-2567.2004.02076.x contributor: fullname: Elkord – ident: ref_10 doi: 10.1186/1471-2164-15-190 – volume: 17 start-page: 391 year: 2019 ident: ref_27 article-title: A Phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) in patients with advanced high-grade ovarian serous carcinoma publication-title: J. Transl. Med. doi: 10.1186/s12967-019-02133-w contributor: fullname: Sarivalasis – volume: 2 start-page: 341 year: 2018 ident: ref_2 article-title: Towards superior dendritic-cell vaccines for cancer therapy publication-title: Nat. Biomed. Eng. doi: 10.1038/s41551-018-0250-x contributor: fullname: Saxena – ident: ref_13 doi: 10.1126/scitranslmed.aao5931 – volume: 10 start-page: 1832 year: 2019 ident: ref_28 article-title: A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients publication-title: Front. Immunol. doi: 10.3389/fimmu.2019.01832 contributor: fullname: Digklia – volume: 547 start-page: 217 year: 2017 ident: ref_4 article-title: An immunogenic personal neoantigen vaccine for patients with melanoma publication-title: Nature doi: 10.1038/nature22991 contributor: fullname: Ott – volume: 59 start-page: 1185 year: 2010 ident: ref_16 article-title: Monophosphoryl lipid A plus IFNgamma maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential publication-title: Cancer Immunol. Immunother. doi: 10.1007/s00262-010-0843-z contributor: fullname: Visser – volume: 36 start-page: 285 year: 2004 ident: ref_18 article-title: Validation of the COSTIM bioassay for dendritic cell potency publication-title: J. Pharm. Biomed. Anal. doi: 10.1016/j.jpba.2004.05.025 contributor: fullname: Shankar – volume: 33 start-page: 352 year: 2010 ident: ref_25 article-title: Dendritic cells generated in clinical grade bags strongly differ in immune functionality when compared with classical DCs generated in plates publication-title: J. Immunother. doi: 10.1097/CJI.0b013e3181cc266b contributor: fullname: Rouas – volume: 22 start-page: 1885 year: 2016 ident: ref_6 article-title: Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-15-1509 contributor: fullname: Tureci – volume: 285 start-page: 293 year: 2004 ident: ref_17 article-title: The COSTIM bioassay: A novel potency test for dendritic cells publication-title: J. Immunol. Methods doi: 10.1016/j.jim.2003.12.008 contributor: fullname: Shankar – volume: 2 start-page: e22664 year: 2013 ident: ref_26 article-title: Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer publication-title: Oncoimmunology doi: 10.4161/onci.22664 contributor: fullname: Kandalaft – volume: 9 start-page: 198 year: 2011 ident: ref_12 article-title: Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate publication-title: J. Transl. Med. doi: 10.1186/1479-5876-9-198 contributor: fullname: Chiang – volume: 19 start-page: 4801 year: 2013 ident: ref_11 article-title: A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: From bench to bedside publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-13-1185 contributor: fullname: Chiang – volume: 463 start-page: 89 year: 2018 ident: ref_21 article-title: Automated closed-system manufacturing of human monocyte-derived dendritic cells for cancer immunotherapy publication-title: J. Immunol. Methods doi: 10.1016/j.jim.2018.09.012 contributor: fullname: Erdmann – volume: 25 start-page: 7145 year: 2007 ident: ref_15 article-title: The clinical grade maturation cocktail monophosphoryl lipid A plus IFNgamma generates monocyte-derived dendritic cells with the capacity to migrate and induce Th1 polarization publication-title: Vaccine doi: 10.1016/j.vaccine.2007.07.031 contributor: fullname: Karsten – volume: 547 start-page: 222 year: 2017 ident: ref_5 article-title: Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer publication-title: Nature doi: 10.1038/nature23003 contributor: fullname: Sahin – volume: 3 start-page: e963424 year: 2014 ident: ref_1 article-title: Trial watch: Dendritic cell-based anticancer therapy publication-title: Oncoimmunology doi: 10.4161/21624011.2014.963424 contributor: fullname: Bloy |
SSID | ssj0000913867 |
Score | 2.2370057 |
Snippet | With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic... |
SourceID | doaj pubmedcentral proquest crossref pubmed |
SourceType | Open Website Open Access Repository Aggregation Database Index Database |
StartPage | 25 |
SubjectTerms | dendritic cell gmp immunotherapy manufacturing tumor lysate vaccine |
SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LaxRBEG4kp1xEEx-jUUqQ4CFDph_TPXPUTWIQV_ewkdyGfqKQzIq7K6z4463unk12g-DFa0_DFFXV1V_RVV8R8lpVzAYhQ4x-bSlqL-MjoSu1rIIJMlDKY6Pw-JM8vxAfLuvLjVFfsSYs0wNnxR1jMGXB6CpoY4RV0oTWytbWXKlGOJuhEa03kqkUg1vKG6kylw_HvP74p7bxpXqOMsV7fusaSmz9f4OYdyslN66eswfk_oAZ4W2W9SG55_s9cjjJpNOrI5je9lDNj-AQJrd01Kt98nujLgh07-AzRonrof0SZgE0vB9PylGqLUc9w1j3y9jvkBoYYegkAAS3uHOyxu6_vIPp8hoXP67miFfhxPcujU2Akb-6gi9ZEY_IxdnpdHReDjMXSivqdlEy7phX2rWOOxqcDJzrIE1dCeMqS43ytmHKO1QwjWM7MP8KaGUX8Bwz6hV_THb6We-fEuBSB1Y7VdlKCC2DboxvaOCeNppSaQvyZm2C7num1ugwJYnW6u5YqyDvoolutkVO7LSAntINntL9y1MK8mpt4A7PUHwY0b2fLecd4ynNa1lTkCfZ4De_whAlMKeiBVFbrrAly_aX_tvXxNOtaK0QbT77H8I_J7ssZvoVLak4IDuLH0v_AuHQwrxMnv8H-rsOwg 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/eLvHCXMwjV1JbxMxFLZKe-GC2JmyyEhVxaED42XsmQNCEGgrRCCHBOU28gqV0glkkqpB_HiePZOmqXLg6rHskd_2fbLfewgdyIwaz4UP3q9Mee5EuCS0qRKZ1154QlhIFO5_Facj_nmcj9ftgLoDbLZSu9BPajSbvL78vXwHBv82ME6g7G8ulAmX0A1sF0L4LbRHOeNB3fsd1o9uuSSsiB1lKXD3lJVs3Jb62bbGRpSKxfy3IdCbDymvRabju-hOBynx-1YH7qEdV99Hh4O2JvXyCA_XKVbNET7Eg3W16uUD9PfasyGsaou_gRM577Iz8dRjhU_6g7QXn56DGHBf1YuQDhHzG3GXaIAB-8LMwQra_3EWDxfnMPhl2QCcxR9dbWNXBdxzkwn-3h7EQzQ6_jTsnaZdS4bU8Lycp5RZ6qSypWWWeCs8Y8oLnWdc28wQLZ0pqHQWDpuErh5AzzwogfVg5pQ4yR6h3XpauycIM6E8za3MTMa5El4V2hXEM0cKRYgwCXq1EkH1q628UQFjCdKqbkgrQR-CiK6mhZLZcWA6-1F1FlhBVKZeq8wrrbmRQvvSiNLkTMqCW6MS9HIl4ApMLNybqNpNF01FWWSBJS0S9LgV-NVW4ME4UC6SILmhChv_svmlPvsZy3hLkksAo_v_se9TdJsGnp-RlPBnaHc-W7jnAIbm-kVU8n_9Rw0Q priority: 102 providerName: Scholars Portal |
Title | Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine |
URI | https://www.ncbi.nlm.nih.gov/pubmed/31947581 https://search.proquest.com/docview/2341617928 https://pubmed.ncbi.nlm.nih.gov/PMC7157441 https://doaj.org/article/6782fba0fabb4c76bf9c69c537784dca |
Volume | 8 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Pb9MwFLa2IaFdEL_JBpWR0MRhWePYsZMjKxsTIiNCHdot8k-Y1KbT2iIV8cfz7CRbO3HikkPiKJbfs9_34vd9RuidSFLtGHd-9StillnuNwlNLHnilOOOEOqJwuU5P7tgny-zyy2U9VyYULSv1dVRM5keNVc_Q23l9VQP-zqxYVWOBMkEhPHhNtoWlK6l6GH5LQjNuWhlfCik9MNfUvtN6jl0x4f4XfQQ_I4BUCYbwSho9v8LaN6vl1wLQKeP0aMOOeIPbQ-foC3bPEUHVSs9vTrE4zsm1fwQH-DqTpR69Qz9WasOwrIx-CusFdOOhIlnDkv8qaziUagwh9HGpWyWnvUQaIy44xNggLjQsuoR_G9r8Hg5hZtfVnNArfijbUw4PAGP7GSCv7dj8hxdnJ6MR2dxd_JCrFlWLOKUmtQKaQpDDXGGO0ql4ypLmDKJJkpYnafCGhhr4g_vgCzMga2Ng9mcEivoC7TTzBr7CmHKpUszIxKdMCa5k7myOXHUklwSwnWE3vcmqK9bgY0aEhNvuPqe4SJ07E1028wrY4cbs5sfdecfNQTf1CmZOKkU04IrV2he6IwKkTOjZYTe9gauYSb57RHZ2NlyXqc0JHtFmkfoZWvw20_1DhMhseEKG33ZfALOG9S6O2fd--8399Fu6pP8hMSEvUY7i5ulfQNIaKEG6MHxyXn1bRD-JMC1ZPkgzIa_9mkRUA |
link.rule.ids | 230,315,733,786,790,870,891,2115,2236,24346,27957,27958,33780,53827,53829 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbGkGAv3AflaiQ08bC0cezYySMURoF29KGb9hb5yqa16bS2SJ348Rw7ydZWvMCr7ShOzudzsc_5jNA7ESfaMe689ssjllruDwlNJHnslOOOEOoLhQeHvHfEvp2kJ1sobWphQtK-Vmftcjxpl2enIbfyYqI7TZ5YZzjoCpIKMOOdW-g2rNdErATpQQHnhGZcVEQ-FIL6zi-p_TH1DCbkjfwOugPIY-AqkzVzFFj7_-ZqbmZMrpigg_vouJl8lXly3l7MVVtfbfA6_vPXPUD3aqcUf6i6H6ItWz5Ce8OK1Xq5j0c3RVqzfbyHhzd818vH6PdK4hGWpcE_QA1N6vpOPHVY4i-DYdQNyesgSDyQ5cIXVIQKSVyXKmDwnmHksAkOrqzBo8UEGvvLGTjE-JMtTbiXAXfteIyPq5_9BB0dfB51e1F9qUOkWZrPo4SaxAppckMNcYY7SqXjKo2ZMrEmSlgNErUGhEj8vSAQ4DmAkXGgKBJiBd1F2-W0tM8Qply6JDUi1jFjkjuZKZsRRy3JJCFct9D7RrbFRcXdUUDM4xFRbCCihT562V8P86TboWF6-bOohVOAXU-ckrGTSjEtuHK55rlOqRAZM1q20NsGOQUsUn_yIks7XcyKhIY4Mk-yFnpaIen6VQ0SW0isYWxtLus9gJxABF4j5fl_P_kG3e2NBv2i__Xw-wu0k_i9hJhEhL1E2_PLhX0FDtdcvQ7L6w9ZWC_c |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLZgSNNeuF_K1Uho4mFp4kvs5BE6yoB15KFD014iX9m0Nq3WFqkTPx7bSba24mmvjqM4OZ_PJT7nOwB84AlWljLrtV8e0dQwf0ioI8ESKy2zCBFfKDw4YgfH9PtJerLS6isk7St53q1G4251fhZyK6djFbd5YnEx6HGUcmfG46m28V1wz-1ZnK8E6kEJ54hkjNdkPsQF9vEfofxR9cwtyhv6HbDt0Eedu4zWTFJg7v-fu7mZNblihvoPwGn7AnX2yUV3MZdddbXB7XirN3wI7jfOKfxUT3kE7pjqMdgtanbr5R4c3hRrzfbgLixueK-XT8DflQQkKCoNfzp1NG7qPOHEQgG_DoqoF5LYnUDhQFQLX1gRKiVhU7IAnRftZhZtkHBlNBwuxm7wcDlzjjHcN5UO_Rlgz4xG8Ff9wZ-C4_6XYe8gapo7RIqm-TzCRGPDhc410chqZgkRlsk0oVInCkluVIa50U6QyPcHcYGedXDS1ikMjAwnz8BWNanMCwAJExanmicqoVQwKzJpMmSJQZlAiKkO-NjKt5zWHB6li308KsoNVHTAZy__62mefDsMTC5_l42ASmffsZUisUJKqjiTNlcsVynhPKNaiQ5436KndJvVn8CIykwWsxKTEE_mOOuA5zWarh_VorED-BrO1tayfsWhJxCCN2h5ees734HtYr9fHn47-vEK7GD_SyFBEaKvwdb8cmHeOL9rLt-GHfYPq14yXA |
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=Development+and+Optimization+of+a+GMP-Compliant+Manufacturing+Process+for+a+Personalized+Tumor+Lysate+Dendritic+Cell+Vaccine&rft.jtitle=Vaccines+%28Basel%29&rft.au=Boudousqui%C3%A9%2C+Caroline&rft.au=Boand%2C+Val%C3%A9rie&rft.au=Lingre%2C+Emilie&rft.au=Dutoit%2C+Laeticia&rft.date=2020-01-14&rft.issn=2076-393X&rft.eissn=2076-393X&rft.volume=8&rft.issue=1&rft_id=info:doi/10.3390%2Fvaccines8010025&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2076-393X&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2076-393X&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2076-393X&client=summon |