TY - JOUR
T1 - Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action
AU - Willsmore, Zena N
AU - Coumbe, Ben G T
AU - Crescioli, Silvia
AU - Reci, Sara
AU - Gupta, Ayushi
AU - Harris, Robert J
AU - Chenoweth, Alicia
AU - Chauhan, Jitesh
AU - Bax, Heather J
AU - McCraw, Alexa
AU - Cheung, Anthony
AU - Osborn, Gabriel
AU - Hoffmann, Ricarda M
AU - Nakamura, Mano
AU - Laddach, Roman
AU - Geh, Jenny L C
AU - Ross, Alastair MacKenzie
AU - Healy, Ciaran
AU - Tsoka, Sophia
AU - Spicer, James F
AU - Josephs, Debra H
AU - Papa, Sophie
AU - Lacy, Katie Elizabeth
AU - Karagiannis, Sophia N
N1 - Funding Information:
The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London (IS‐BRC‐1215‐20006) (SNK, JFS, SP, KEL). The authors acknowledge support by the Medical Research Council (MR/L023091/1) (SNK, JFS); Breast Cancer Now (147; KCL‐BCN‐Q3) (SNK); the Cancer Research UK King's Health Partners Centre at King's College London (C604/A25135) (SNK, JFS, SP, ZNW); The Guy's and St Thomas's Foundation Trust Charity (Melanoma Special Fund, 573) (KEL, SNK); CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587) (JFS); Cancer Research UK (C30122/A11527; C30122/A15774) (JFS, SNK, HJB). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101212511&partnerID=8YFLogxK
U2 - 10.1002/eji.202048747
DO - 10.1002/eji.202048747
M3 - Review article
C2 - 33450785
SN - 0014-2980
VL - 51
SP - 544
EP - 556
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -