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Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action |
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| Authors: | Zena N Willsmore Ben G T Coumbe Silvia Crescioli Sara Reci Ayushi Gupta Robert J Harris Alicia Chenoweth Jitesh Chauhan Heather J Bax Alexa McCraw Anthony Cheung Gabriel Osborn Ricarda M Hoffmann Mano Nakamura Roman Laddach Jenny L C Geh Alastair MacKenzie-Ross Ciaran Healy Sophia Tsoka James F Spicer Debra H Josephs Sophie Papa Katie E Lacy Sophia N Karagiannis |
| Institution: | 1. St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT United Kingdom;2. St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT United Kingdom
Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King's College London, Guy's Cancer Centre, London, United Kingdom;3. St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT United Kingdom School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom;4. St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT United Kingdom Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, London, United Kingdom;5. Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom;6. Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, London, United Kingdom;7. School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom;8. Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom ImmunoEngineering, School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom |
| Abstract: | 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. |
| Keywords: | PD-1 CTLA-4 Cancer Immunotherapy Melanoma |