TY - JOUR
T1 - AntiCTLA-4 antibody therapy
T2 - Immune monitoring during clinical development of a novel immunotherapy
AU - Callahan, Margaret K.
AU - Wolchok, Jedd D.
AU - Allison, James P.
PY - 2010/10
Y1 - 2010/10
N2 - Cytotoxic T-lymphocyte-associated antigen (CTLA-4), also known as CD152, is a co-inhibitory molecule that functions to regulate T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Two CTLA-4blocking antibodies are presently under clinical investigation: ipilimumab and tremelimumab. CTLA-4 blockade has shown promise in treatment of patients with metastatic melanoma, with a recently completed randomized, double-blind phase III trial demonstrating a benefit in overall survival (OS) in the treated population. However, this approach appears to benefit only a subset of patients. Understanding the mechanism(s) of action of CTLA-4 blockade and identifying prognostic immunologic correlates of clinical endpoints to monitor are presently areas of intense investigation. Several immunologic endpoints have been proposed to correlate with clinical activity. This review will focus on the endpoints of immune monitoring described in studies to date and discuss future areas of additional work needed.
AB - Cytotoxic T-lymphocyte-associated antigen (CTLA-4), also known as CD152, is a co-inhibitory molecule that functions to regulate T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Two CTLA-4blocking antibodies are presently under clinical investigation: ipilimumab and tremelimumab. CTLA-4 blockade has shown promise in treatment of patients with metastatic melanoma, with a recently completed randomized, double-blind phase III trial demonstrating a benefit in overall survival (OS) in the treated population. However, this approach appears to benefit only a subset of patients. Understanding the mechanism(s) of action of CTLA-4 blockade and identifying prognostic immunologic correlates of clinical endpoints to monitor are presently areas of intense investigation. Several immunologic endpoints have been proposed to correlate with clinical activity. This review will focus on the endpoints of immune monitoring described in studies to date and discuss future areas of additional work needed.
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U2 - 10.1053/j.seminoncol.2010.09.001
DO - 10.1053/j.seminoncol.2010.09.001
M3 - Article
C2 - 21074063
AN - SCOPUS:78449243490
SN - 0093-7754
VL - 37
SP - 473
EP - 484
JO - Seminars in oncology
JF - Seminars in oncology
IS - 5
ER -