Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy

被引:133
作者
Zhao, Yinghao [1 ]
Yang, Wei [1 ]
Huang, Yuanyuan [2 ]
Cui, Ranji [1 ]
Li, Xiangyan [3 ]
Li, Bingjin [1 ]
机构
[1] Jilin Univ, Hosp 2, Jilin Prov Key Lab Mol & Chem Genet, Changchun, Jilin, Peoples R China
[2] Jilin Univ, Hosp 1, Dept Pediat, Changchun, Jilin, Peoples R China
[3] Changchun Univ Chinese Med, Affiliated Hosp, Jilin Prov Key Lab BioMacromol Chinese Med, Jilin Ginseng Acad, Changchun, Jilin, Peoples R China
关键词
Ctla-4; PD-1; Antibody; ipilimumab; Tremelimumab; CELL LUNG-CANCER; RESISTANT PROSTATE-CANCER; T-CELLS; ADVERSE EVENTS; RS231775; POLYMORPHISM; ANTI-CTLA-4; ANTIBODY; DOUBLE-BLIND; HEPATOCELLULAR-CARCINOMA; LYMPHOCYTE MOLECULES; BIOLOGICAL FUNCTION;
D O I
10.1159/000490025
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a membrane glycoprotein expressed by activated effector T cells (Teffs) and participates in the repression of T cell proliferation, cell cycle progression and cytokine production. Currently, antibodies targeting CTLA-4, ipilimumab and tremelimumab are widely used as a therapeutic approach in a variety of human malignancies. However, their detailed mechanism remains unclear. Therefore, in this review, we focused specifically on recent findings concerning the role of CTLA-4 in immune response and also discussed clinical studies of targeting CTLA-4, alone or in combination with other therapies for the treatment of cancers. CTLA-4 blockade is used as a therapeutic approach for the treatment of cancer through competing with CD28-positive costimulation for binding to their shared B7 ligands or exhibiting direct inhibitory effect on signaling molecules in the cytoplasmic tail. At present, antibodies for targeting CTLA-4 or in combination with other therapies significantly reinforced the anti-tumor effect and improved the prognosis of malignant disease. In addition, severe adverse events of targeting CTLA-4 therapy could be a challenge for the development of this therapeutic strategy. This review may provide some new insights for clinical studies of targeting CTLA-4. (c) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:721 / 734
页数:14
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