TY - GEN
T1 - The Role of Neoantigens in Naturally Occurring and Therapeutically Induced Immune Responses to Cancer
AU - Ward, Jeffrey P.
AU - Gubin, Matthew M.
AU - Schreiber, Robert D.
N1 - Funding Information:
We are grateful to T. Noguchi for constructive criticism and comments. R.D.S. receives research support from the National Cancer Institute (RO1 CA043059, RO1 CA190700, U01 CA141541), the Cancer Research Institute, the WWWW Foundation, the Siteman Cancer Center/Barnes-Jewish Hospital (Cancer Frontier Fund), Bristol-Myers Squibb Inc., Janssen and Stand Up to Cancer. J.P.W. is supported by a T32 training grant in hematology (5T32HL007088-40) from the National Heart, Lung, and Blood Institute. M.M.G. is supported by a postdoctoral training grant (Irvington Postdoctoral Fellowship) from the Cancer Research Institute.
PY - 2016
Y1 - 2016
N2 - Definitive experimental evidence from mouse cancer models and strong correlative clinical data gave rise to the Cancer Immunoediting concept that explains the dual host-protective and tumor-promoting actions of immunity on developing cancers. Tumor-specific neoantigens can serve as targets of spontaneously arising adaptive immunity to cancer and thereby determine the ultimate fate of developing tumors. Tumor-specific neoantigens can also function as optimal targets of cancer immunotherapy against established tumors. These antigens are derived from nonsynonymous mutations that occur during cellular transformation and, because they are foreign to the host genome, are not subject to central tolerance. In this review, we summarize the experimental evidence indicating that cancer neoantigens are the source of both spontaneously occurring and therapeutically induced immune responses against cancer. We also review the advances in genomics, bioinformatics, and cancer immunotherapy that have facilitated identification of neoantigens and have moved personalized cancer immunotherapies into clinical trials, with the promise of providing more specific, safer, more effective, and perhaps even more generalizable treatments to cancer patients than current immunotherapies.
AB - Definitive experimental evidence from mouse cancer models and strong correlative clinical data gave rise to the Cancer Immunoediting concept that explains the dual host-protective and tumor-promoting actions of immunity on developing cancers. Tumor-specific neoantigens can serve as targets of spontaneously arising adaptive immunity to cancer and thereby determine the ultimate fate of developing tumors. Tumor-specific neoantigens can also function as optimal targets of cancer immunotherapy against established tumors. These antigens are derived from nonsynonymous mutations that occur during cellular transformation and, because they are foreign to the host genome, are not subject to central tolerance. In this review, we summarize the experimental evidence indicating that cancer neoantigens are the source of both spontaneously occurring and therapeutically induced immune responses against cancer. We also review the advances in genomics, bioinformatics, and cancer immunotherapy that have facilitated identification of neoantigens and have moved personalized cancer immunotherapies into clinical trials, with the promise of providing more specific, safer, more effective, and perhaps even more generalizable treatments to cancer patients than current immunotherapies.
KW - Cancer Immunoediting
KW - Cancer immunotherapy
KW - Checkpoint blockade immunotherapy
KW - Neoantigens
KW - Tumor-specific mutant antigens
UR - http://www.scopus.com/inward/record.url?scp=84957928309&partnerID=8YFLogxK
U2 - 10.1016/bs.ai.2016.01.001
DO - 10.1016/bs.ai.2016.01.001
M3 - Conference contribution
C2 - 26922999
AN - SCOPUS:84957928309
SN - 9780128051566
T3 - Advances in Immunology
SP - 25
EP - 74
BT - Tumor Immunology, 2016
A2 - Schreiber, Robert D.
PB - Academic Press Inc.
ER -