Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action

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 Elizabeth Lacy; Sophia N Karagiannis

doi:10.1002/eji.202048747

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action

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 Elizabeth Lacy, Sophia N Karagiannis

St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, U.K.
School of Basic & Medical Biosciences
King's College London
School of Cancer & Pharmaceutical Sciences, King's College London, 9th Floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK.
Breast Cancer Now
School of Cancer & Pharmaceutical Sciences
Guy's Comprehensive Cancer Centre
Informatics Department
Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, London, United Kingdom.
King's College and St Thomas' Hospitals
GSTT Guy's and St Thomas' NHS Foundation Trust
ImmunoEngineering Group

Research output: Contribution to journal › Review article › peer-review

183 Citations (Scopus)

828 Downloads (Pure)

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.

Original language	English
Pages (from-to)	544-556
Number of pages	13
Journal	European Journal of Immunology
Volume	51
Issue number	3
Early online date	15 Jan 2021
DOIs	https://doi.org/10.1002/eji.202048747
Publication status	Published - Mar 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1002/eji.202048747

Willsmore et al eji.202048747Final published version, 1.46 MBLicence: CC BY

Cite this

Willsmore, Z. N., Coumbe, B. G. T., Crescioli, S., Reci, S., Gupta, A., Harris, R. J., Chenoweth, A., Chauhan, J., Bax, H. J., McCraw, A., Cheung, A., Osborn, G., Hoffmann, R. M., Nakamura, M., Laddach, R., Geh, J. L. C., Ross, A. M., Healy, C., Tsoka, S., ... Karagiannis, S. N. (2021). Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action. European Journal of Immunology, 51(3), 544-556. https://doi.org/10.1002/eji.202048747

@article{7a13e408ee424709830dc4d11c2913df,

title = "Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action",

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.",

author = "Willsmore, \{Zena N\} and Coumbe, \{Ben G T\} and Silvia Crescioli and Sara Reci and Ayushi Gupta and Harris, \{Robert J\} and Alicia Chenoweth and Jitesh Chauhan and Bax, \{Heather J\} and Alexa McCraw and Anthony Cheung and Gabriel Osborn and Hoffmann, \{Ricarda M\} and Mano Nakamura and Roman Laddach and Geh, \{Jenny L C\} and Ross, \{Alastair MacKenzie\} and Ciaran Healy and Sophia Tsoka and Spicer, \{James F\} and Josephs, \{Debra H\} and Sophie Papa and Lacy, \{Katie Elizabeth\} and Karagiannis, \{Sophia N\}",

note = "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: {\textcopyright} 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

doi = "10.1002/eji.202048747",

language = "English",

volume = "51",

pages = "544--556",

journal = "European Journal of Immunology",

issn = "0014-2980",

publisher = "Wiley-VCH Verlag",

number = "3",

}

Willsmore, ZN, Coumbe, BGT, Crescioli, S, Reci, S, Gupta, A, Harris, RJ , Chenoweth, A, Chauhan, J, Bax, HJ , McCraw, A , Cheung, A , Osborn, G , Hoffmann, RM , Nakamura, M , Laddach, R, Geh, JLC, Ross, AM, Healy, C, Tsoka, S , Spicer, JF , Josephs, DH , Papa, S, Lacy, KE & Karagiannis, SN 2021, 'Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action', European Journal of Immunology, vol. 51, no. 3, pp. 544-556. https://doi.org/10.1002/eji.202048747

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 - https://www.scopus.com/pages/publications/85101212511

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 -

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this