Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma.

Autor:	Khair DO; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Bax HJ; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom., Mele S; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Crescioli S; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Pellizzari G; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Khiabany A; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Nakamura M; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Harris RJ; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom.; Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, Guy's Cancer Centre, King's College London, London, United Kingdom.; Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom., French E; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Hoffmann RM; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom., Williams IP; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Cheung A; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.; Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, Guy's Cancer Centre, King's College London, London, United Kingdom., Thair B; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Beales CT; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Touizer E; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Signell AW; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Tasnova NL; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Spicer JF; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom., Josephs DH; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom., Geh JL; Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom., MacKenzie Ross A; Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom., Healy C; Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom., Papa S; School of Cancer & Pharmaceutical Sciences, Guy's Hospital, King's College London, London, United Kingdom., Lacy KE; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom., Karagiannis SN; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Guy's Hospital, King's College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Mar 19; Vol. 10, pp. 453. Date of Electronic Publication: 2019 Mar 19 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.00453
Abstrakt:	The immune system employs several checkpoint pathways to regulate responses, maintain homeostasis and prevent self-reactivity and autoimmunity. Tumor cells can hijack these protective mechanisms to enable immune escape, cancer survival and proliferation. Blocking antibodies, designed to interfere with checkpoint molecules CTLA-4 and PD-1/PD-L1 and counteract these immune suppressive mechanisms, have shown significant success in promoting immune responses against cancer and can result in tumor regression in many patients. While inhibitors to CTLA-4 and the PD-1/PD-L1 axis are well-established for the clinical management of melanoma, many patients do not respond or develop resistance to these interventions. Concerted efforts have focused on combinations of approved therapies aiming to further augment positive outcomes and survival. While CTLA-4 and PD-1 are the most-extensively researched targets, results from pre-clinical studies and clinical trials indicate that novel agents, specific for checkpoints such as A2AR, LAG-3, IDO and others, may further contribute to the improvement of patient outcomes, most likely in combinations with anti-CTLA-4 or anti-PD-1 blockade. This review discusses the rationale for, and results to date of, the development of inhibitory immune checkpoint blockade combination therapies in melanoma. The clinical potential of new pipeline therapeutics, and possible future therapy design and directions that hold promise to significantly improve clinical prognosis compared with monotherapy, are discussed.
Databáze:	MEDLINE
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