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
[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.
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