Immunoregulatory antigens-novel targets for cancer immunotherapy

TY - JOUR

T1 - Immunoregulatory antigens-novel targets for cancer immunotherapy

AU - Pedersen, Ayako Wakatsuki

AU - Kopp, Katharina L

AU - Andersen, Mads Hald

AU - Zocca, Mai-Britt

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1. Vaccination approaches to potentiate these T cells have proven safe with minimal toxicity in the clinical phase I trials conducted thus far. Given that immunoregulatory antigens can be new targets for cancer immunotherapy, we propose here that they could be considered as a new class of tumor antigens. Targeting such antigens has advantages over targeting classical tumor antigens, as there is no requirement for identification of relevant antigens that are specific for the cancer type, and the targets are genetically stable. Furthermore, targeting immunoregulatory antigen-specific T cells potentially has dual mode of actions (I) targeting immune suppression and thereby potentiating anti-tumor effector T cell responses and (II) direct killing of immunoregulatory antigen-expressing tumor cells.

AB - Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1. Vaccination approaches to potentiate these T cells have proven safe with minimal toxicity in the clinical phase I trials conducted thus far. Given that immunoregulatory antigens can be new targets for cancer immunotherapy, we propose here that they could be considered as a new class of tumor antigens. Targeting such antigens has advantages over targeting classical tumor antigens, as there is no requirement for identification of relevant antigens that are specific for the cancer type, and the targets are genetically stable. Furthermore, targeting immunoregulatory antigen-specific T cells potentially has dual mode of actions (I) targeting immune suppression and thereby potentiating anti-tumor effector T cell responses and (II) direct killing of immunoregulatory antigen-expressing tumor cells.

KW - Antigens, Neoplasm/immunology

KW - Humans

KW - Immunotherapy/methods

U2 - 10.21037/cco.2018.01.03

DO - 10.21037/cco.2018.01.03

M3 - Journal article

C2 - 29764164

SN - 2304-3865

VL - 7

SP - 1

EP - 8

JO - Chinese Clinical Oncology

JF - Chinese Clinical Oncology

IS - 2

M1 - 19

ER -