TY - JOUR
T1 - Tumor neoantigens
T2 - Building a framework for personalized cancer immunotherapy
AU - Gubin, Matthew M.
AU - Artyomov, Maxim N.
AU - Mardis, Elaine R.
AU - Schreiber, Robert D.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably durable responses in some patients has been ascribed in part to T cells that can (a) kill tumor cells directly, (b) orchestrate diverse antitumor immune responses, (c) manifest long-lasting memory, and (d) display remarkable specificity for tumor-derived proteins. This specificity stems from fundamental differences between cancer cells and their normal counterparts in that the former develop proteinaltering mutations and undergo epigenetic and genetic alterations, resulting in aberrant protein expression. These events can result in formation of tumor antigens. The identification of mutated and aberrantly expressed self-Tumor antigens has historically been time consuming and laborious. While mutant antigens are usually expressed in a tumor-specific manner, aberrantly expressed antigens are often shared between cancers and, therefore, in the past, have been the major focus of therapeutic cancer vaccines. However, advances in next-generation sequencing and epitope prediction now permit the rapid identification of mutant tumor neoantigens. This review focuses on a discussion of mutant tumor neoantigens and their use in personalizing cancer immunotherapies.
AB - It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably durable responses in some patients has been ascribed in part to T cells that can (a) kill tumor cells directly, (b) orchestrate diverse antitumor immune responses, (c) manifest long-lasting memory, and (d) display remarkable specificity for tumor-derived proteins. This specificity stems from fundamental differences between cancer cells and their normal counterparts in that the former develop proteinaltering mutations and undergo epigenetic and genetic alterations, resulting in aberrant protein expression. These events can result in formation of tumor antigens. The identification of mutated and aberrantly expressed self-Tumor antigens has historically been time consuming and laborious. While mutant antigens are usually expressed in a tumor-specific manner, aberrantly expressed antigens are often shared between cancers and, therefore, in the past, have been the major focus of therapeutic cancer vaccines. However, advances in next-generation sequencing and epitope prediction now permit the rapid identification of mutant tumor neoantigens. This review focuses on a discussion of mutant tumor neoantigens and their use in personalizing cancer immunotherapies.
UR - http://www.scopus.com/inward/record.url?scp=84941710020&partnerID=8YFLogxK
U2 - 10.1172/JCI80008
DO - 10.1172/JCI80008
M3 - Review article
C2 - 26258412
AN - SCOPUS:84941710020
SN - 0021-9738
VL - 125
SP - 3413
EP - 3421
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
ER -