A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice
Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induce...
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Published in | Oncoimmunology Vol. 7; no. 5; p. e1421890 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Taylor & Francis
04.05.2018
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Abstract | Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4
+
, CD8
+
, and IFN-γ
+
CD8
+
T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu−) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer. |
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AbstractList | Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4
+
, CD8
+
, and IFN-γ
+
CD8
+
T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu−) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer. Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4 , CD8 , and IFN-γ CD8 T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu-) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer. Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4+, CD8+, and IFN-γ+CD8+ T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu−) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer. |
Author | Choi, Jae-Hyeog Lee, Ji-Young Choi, Il-Whan Lee, Anbok Song, Joo Yeon Park, Seung Jae Roh, Kug-Hwan Kim, Ilhwan Fu, Yang-Xin Kim, Ki Hyang Jung, Hana Park, SaeGwang Lee, Won-Sik Seo, Su-Kil Yea, Sung Su |
Author_xml | – sequence: 1 givenname: Jae-Hyeog surname: Choi fullname: Choi, Jae-Hyeog organization: Department of Microbiology and Immunology, Inje University College of Medicine – sequence: 2 givenname: Ki Hyang surname: Kim fullname: Kim, Ki Hyang organization: Department of Internal Medicine, Inje University College of Medicine – sequence: 3 givenname: Kug-Hwan surname: Roh fullname: Roh, Kug-Hwan organization: Department of Microbiology and Immunology, Inje University College of Medicine – sequence: 4 givenname: Hana surname: Jung fullname: Jung, Hana organization: Department of Microbiology and Immunology, Inje University College of Medicine – sequence: 5 givenname: Anbok surname: Lee fullname: Lee, Anbok organization: Department of Surgery, Inje University College of Medicine – sequence: 6 givenname: Ji-Young orcidid: 0000-0002-3279-7865 surname: Lee fullname: Lee, Ji-Young organization: Department of Internal Medicine, Inje University College of Medicine – sequence: 7 givenname: Joo Yeon surname: Song fullname: Song, Joo Yeon organization: Department of Pathology, Dongnam Institute of Radiological and Medical Sciences – sequence: 8 givenname: Seung Jae surname: Park fullname: Park, Seung Jae organization: Department of Internal Medicine, Inje University College of Medicine – sequence: 9 givenname: Ilhwan orcidid: 0000-0003-4166-6303 surname: Kim fullname: Kim, Ilhwan organization: Department of Internal Medicine, Inje University College of Medicine – sequence: 10 givenname: Won-Sik surname: Lee fullname: Lee, Won-Sik organization: Department of Internal Medicine, Inje University College of Medicine – sequence: 11 givenname: Su-Kil surname: Seo fullname: Seo, Su-Kil organization: Department of Microbiology and Immunology, Inje University College of Medicine – sequence: 12 givenname: Il-Whan surname: Choi fullname: Choi, Il-Whan organization: Department of Microbiology and Immunology, Inje University College of Medicine – sequence: 13 givenname: Yang-Xin surname: Fu fullname: Fu, Yang-Xin organization: The Department of Pathology and Immunology, University of Texas Southwestern Medical Center – sequence: 14 givenname: Sung Su surname: Yea fullname: Yea, Sung Su email: ssyea@inje.ac.kr organization: Department of Biochemistry, Inje University College of Medicine – sequence: 15 givenname: SaeGwang surname: Park fullname: Park, SaeGwang email: micpsg@inje.ac.kr organization: Department of Microbiology and Immunology, Inje University College of Medicine |
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Cites_doi | 10.1016/j.bmcl.2013.05.007 10.1371/journal.pone.0099486 10.4049/jimmunol.165.9.5133 10.1056/NEJMoa052122 10.1038/ni0403-313 10.1016/j.ctrv.2013.09.002 10.1038/nrd1902 10.3389/fonc.2012.00062 10.1007/s10549-012-2369-x 10.1200/JCO.2007.11.6699 10.1158/1078-0432.CCR-13-1777 10.1186/1471-2407-14-647 10.1056/NEJMra043186 10.1016/j.ccr.2010.06.014 10.1210/jc.2011-1426 10.1200/JCO.2011.37.4207 10.1126/science.3798106 10.1200/JCO.2011.36.1360 10.6004/jnccn.2013.0098 10.1200/JCO.2009.25.3641 10.1158/2159-8290.CD-16-0716 10.3389/fimmu.2012.00244 10.3389/fimmu.2012.00245 10.1073/pnas.1016569108 10.1074/jbc.M112.379446 10.3389/fimmu.2013.00020 10.1158/1078-0432.CCR-13-2769 10.1158/1078-0432.CCR-12-0714 10.1158/1078-0432.CCR-12-2522 10.3389/fimmu.2012.00247 10.1038/nrc3860 10.1016/j.ccr.2009.03.020 10.1038/nrm2882 10.1158/1078-0432.CCR-14-0947 10.1200/JCO.2008.21.4437 10.1016/j.breast.2015.06.002 10.1101/gad.191973.112 10.1200/JCO.2002.20.3.719 10.1101/gad.216069.113 10.2147/OTT.S89967 |
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References | cit0011 cit0033 cit0012 cit0034 cit0010 cit0032 cit0030 Okkenhaug K (cit0015) 2010; 346 cit0019 cit0017 cit0039 cit0018 cit0037 cit0016 cit0038 cit0013 cit0035 cit0014 cit0036 cit0022 cit0001 cit0023 cit0020 cit0042 cit0021 cit0040 cit0041 Mayer I. (cit0031) 2013; 11 cit0008 cit0009 cit0006 cit0028 cit0007 cit0029 cit0004 cit0026 cit0005 cit0027 cit0002 cit0024 cit0003 cit0025 |
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Title | A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice |
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