How Does an Anti-CTLA-4 Antibody Promote Cancer Immunity?

Yang Liu ¹, Pan Zheng ²

Affiliations

¹ Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland Baltimore School of Medicine, Baltimore, MD 21201, USA. Electronic address: yaliu@ihv.umaryland.edu.
² Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland Baltimore School of Medicine, Baltimore, MD 21201, USA. Electronic address: pzheng@ihv.umaryland.edu.

PMID: 30497614
18 References
24 citations

Abstract

Anti-CTLA-4 antibodies can induce lasting protection for some melanoma patients. However, their therapeutic potential is limited by significant immunotherapy-related adverse effects (irAE). Here, we argue that the therapeutic effect may be based on an agonist activity that is fundamentally distinct, and can be therapeutically differentiated, from the antagonist activity responsible for irAE.

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References
Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. S Onizuka, I Tawara, +3 authors, J Shimizu, S Sakaguchi, T Fujita, E Nakayama. less Cancer Res, 1999 Jul 09; 59(13). PMID: 10397255 Highly Cited.
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Giao Q Phan, James C Yang, +14 authors, Steven A Rosenberg. less Proc Natl Acad Sci U S A, 2003 Jun 27; 100(14). PMID: 12826605 Free PMC article. Highly Cited.
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Tyler J Curiel, George Coukos, +18 authors, Weiping Zou. less Nat Med, 2004 Aug 24; 10(9). PMID: 15322536 Highly Cited.
Checkpoint blockade in cancer immunotherapy. Alan J Korman, Karl S Peggs, James P Allison. Adv Immunol, 2006 May 30; 90. PMID: 16730267 Free PMC article. Highly Cited. Review.
Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Chunxia Chen, Emily A Rowell, +2 authors, Rajan M Thomas, Wayne W Hancock, Andrew D Wells. less J Biol Chem, 2006 Oct 10; 281(48). PMID: 17028180
CTLA-4 control over Foxp3+ regulatory T cell function. Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi. less Science, 2008 Oct 11; 322(5899). PMID: 18845758 Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma. F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba. less N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992 Free PMC article. Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982 Free PMC article. Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman. less Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248 Highly Cited.
Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Hye Sun Kuehn, Weiming Ouyang, +33 authors, Gulbu Uzel. less Science, 2014 Sep 13; 345(6204). PMID: 25213377 Free PMC article. Highly Cited.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok. less N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431 Free PMC article. Highly Cited.
Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Xuexiang Du, Mingyue Liu, +8 authors, Pan Zheng. less Cell Res, 2018 Feb 22; 28(4). PMID: 29463898 Free PMC article. Highly Cited.
A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Xuexiang Du, Fei Tang, +14 authors, Yang Liu. less Cell Res, 2018 Feb 24; 28(4). PMID: 29472691 Free PMC article. Highly Cited.
Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens. Jeremy D Waight, Dhan Chand, +14 authors, Nicholas S Wilson. less Cancer Cell, 2018 Jun 13; 33(6). PMID: 29894690 Free PMC article.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma. less Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281 Free PMC article. Highly Cited.
Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. P Waterhouse, J M Penninger, +6 authors, T W Mak. less Science, 1995 Nov 10; 270(5238). PMID: 7481803 Highly Cited.
CTLA-4 can function as a negative regulator of T cell activation. T L Walunas, D J Lenschow, +5 authors, J A Bluestone. less Immunity, 1994 Aug 01; 1(5). PMID: 7882171 Highly Cited.

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Structure of CTLA-4 complexed with a pH-sensitive cancer immunotherapeutic antibody. Han Gao, Haiyan Cai, +7 authors, Aiwu Zhou. less Cell Discov, 2020 Dec 11; 6(1). PMID: 33298884 Free PMC article.
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Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey. Mohamed A ElTanbouly, Randolph J Noelle. Nat Rev Immunol, 2020 Oct 21; 21(4). PMID: 33077935 Review.
Adverse events induced by immune checkpoint inhibitors. Ana Luisa Perdigoto, Harriet Kluger, Kevan C Herold. Curr Opin Immunol, 2021 Mar 01; 69. PMID: 33640598 Free PMC article. Review.
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Signal pathways of melanoma and targeted therapy. Weinan Guo, Huina Wang, Chunying Li. Signal Transduct Target Ther, 2021 Dec 21; 6(1). PMID: 34924562 Free PMC article. Review.
Developing and characterizing a single-domain antibody (nanobody) against human cytotoxic T-lymphocyte-associated protein 4 (hCTLA-4). Nazli Sotoudeh, Zahra Noormohammadi, +2 authors, Mahdi Behdani. less Iran J Basic Med Sci, 2022 Jan 28; 24(9). PMID: 35083014 Free PMC article.
Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events. Remo Poto, Teresa Troiani, +4 authors, Gilda Varricchi. less Front Immunol, 2022 Apr 19; 13. PMID: 35432346 Free PMC article. Review.
Dissecting the Role of Immune Checkpoint Regulation Patterns in Tumor Microenvironment and Prognosis of Gastric Cancer. Zili Zhen, Zhemin Shen, Peilong Sun. Front Genet, 2022 May 07; 13. PMID: 35518357 Free PMC article.
Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy. Yang Zhou, Miao Li, +7 authors, Lili Yang. less Cancers (Basel), 2022 May 15; 14(9). PMID: 35565395 Free PMC article. Review.

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