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Modulation of CTLA-4 and GITR for Cancer Immunotherapy

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Cancer Immunology and Immunotherapy

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 344))

Abstract

The rational manipulation of antigen-specific T cells to reignite a tumor-specific immune response in cancer patients is a challenge for cancer immunotherapy. Targeting coinhibitory and costimulatory T cell receptors with specific antibodies in cancer patients is an emerging approach to T cell manipulation, namely “immune modulation.” Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor family receptor (GITR) are potential targets for immune modulation through anti-CTLA-4 blocking antibodies and anti-GITR agonistic antibodies, respectively. In this review, we first discuss preclinical findings key to the understanding of the mechanisms of action of these immunomodulatory antibodies and the preclinical evidence of antitumor activity which preceded translation into the clinic. We next describe the outcomes and immune related adverse effects associated with anti-CTLA-4 based clinical trials with particular emphasis on specific biomarkers used to elucidate the mechanisms of tumor immunity in patients. The experience with anti-CTLA-4 therapy and the durable clinical benefit observed provide proof of principle to effective antitumor immune modulation and the promise of future clinical immune modulatory antibodies.

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Acknowledgments

The authors would like to thank Dr. Stephanie Terzulli and Brian Ginsberg for reviewing the manuscript and Drs. Lloyd Old and David Page for their scientific guidance and assistance in generating the immunogram.

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Authors and Affiliations

  1. Immunology Program, Sloan-Kettering Institute, New York, NY, 10065, USA

    Francesca Avogadri, Jianda Yuan, Arvin Yang, David Schaer & Jedd D. Wolchok

  2. Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY, 10065, USA

    Jianda Yuan, Arvin Yang & Jedd D. Wolchok

  3. Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Arvin Yang & Jedd D. Wolchok

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  1. Francesca Avogadri
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  2. Jianda Yuan
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  3. Arvin Yang
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  4. David Schaer
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  5. Jedd D. Wolchok
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Correspondence to Jedd D. Wolchok .

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  1. , Medical Oncology/Hematologic Neoplasial, Dana-Farber Cancer Institute, Binney Street 44, Boston, 02115, Massachusetts, USA

    Glenn Dranoff

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Avogadri, F., Yuan, J., Yang, A., Schaer, D., Wolchok, J.D. (2010). Modulation of CTLA-4 and GITR for Cancer Immunotherapy. In: Dranoff, G. (eds) Cancer Immunology and Immunotherapy. Current Topics in Microbiology and Immunology, vol 344. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2010_49

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