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Войти в исследования European journal of immunology · 2021
Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action.
СтатьяПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод пока не подготовлен
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Willsmore Zena N, Coumbe Ben G T, Crescioli Silvia, Reci Sara, Gupta Ayushi, Harris Robert J, Chenoweth Alicia, Chauhan Jitesh, Bax Heather J, McCraw Alexa, Cheung Anthony, Osborn Gabriel, Hoffmann Ricarda M, Nakamura Mano, Laddach Roman, Geh Jenny L C, MacKenzie-Ross Alastair, Healy Ciaran, Tsoka Sophia, Spicer James F, Josephs Debra H, Papa Sophie, Lacy Katie E, Karagiannis Sophia N
Аннотация
Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.