Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations

Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunother...

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Published in:	Frontiers in oncology Vol. 8; p. 86
Main Authors:	Seidel, Judith A., Otsuka, Atsushi, Kabashima, Kenji
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 28.03.2018
Subjects:	biomarkers cancer immune checkpoint inhibitors immunotherapy melanoma Oncology side effects mode of action biomarkers immunotherapy melanoma side effects cancer immune checkpoint inhibitors
ISSN:	2234-943X, 2234-943X
Online Access:	Get full text
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Abstract	Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the "magic bullet" to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers.
AbstractList	Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the “magic bullet” to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers. Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the "magic bullet" to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers.Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the "magic bullet" to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers.
Author	Seidel, Judith A. Kabashima, Kenji Otsuka, Atsushi
AuthorAffiliation	1 Department of Dermatology, Kyoto University Graduate School of Medicine , Kyoto , Japan 2 Singapore Immunology Network (SIgN), Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Biopolis , Singapore , Singapore
AuthorAffiliation_xml	– name: 1 Department of Dermatology, Kyoto University Graduate School of Medicine , Kyoto , Japan – name: 2 Singapore Immunology Network (SIgN), Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Biopolis , Singapore , Singapore
Author_xml	– sequence: 1 givenname: Judith A. surname: Seidel fullname: Seidel, Judith A. – sequence: 2 givenname: Atsushi surname: Otsuka fullname: Otsuka, Atsushi – sequence: 3 givenname: Kenji surname: Kabashima fullname: Kabashima, Kenji
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29644214$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Copyright	Copyright © 2018 Seidel, Otsuka and Kabashima. 2018 Seidel, Otsuka and Kabashima
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Keywords	mode of action biomarkers immunotherapy melanoma side effects cancer immune checkpoint inhibitors
Language	English
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10.1007/s10120-014-0440-5
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Snippet	Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances...
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StartPage	86
SubjectTerms	biomarkers cancer immune checkpoint inhibitors immunotherapy melanoma Oncology side effects
Title	Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
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