Present and future of immune checkpoint blockade: Monotherapy to adjuvant approaches
Present and future of immune checkpoint blockade: Monotherapy to adjuvant approaches作者机构：Department of Neurosurgery the Johns Hopkins University School of Medicine Department of Oncology the Johns Hopkins University School of Medicine
出 版 物：《World Journal of Immunology》 (世界免疫学杂志)
年 卷 期：2015年第5卷第1期
页 面：1-15页
学科分类：12[管理学] 1204[管理学-公共管理] 120402[管理学-社会医学与卫生事业管理(可授管理学、医学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 10[医学]
主 题：Programmed death-1 Cytotoxic T lymphocyte associated antigen-4 Ipilimumab Nivolumab Immune checkpoint
摘 要：Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include programmed death-1(PD-1), cytotoxic T lymphocyte associated antigen-4(CTLA-4), lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, Glucocorticoid-induced TNFR family-related receptor(GITR), and killer cell immunoglobulin like receptor. With the exception of GITR, after binding to their respective ligands these checkpoints induce down-modulation of immune responses to prevent autoimmunity. However, such immune mechanisms are co-opted by tumors to allow rapid tumor cell proliferation. Pre-clinical studies in antibody blockade of PD-1 and CTLA-4 have led to promising augmentation of effector immune responses in murine tumor models, and human antibodies against PD-1 and CTLA-4 alone or in combination have demonstrated tumor regression in clinical trials. The development of immune checkpoint blockade as a potential future immunotherapy has led to increasing interest in combining treatment modalities. Combination checkpoint blockade with chemotherapy and radiation therapy has shown synergistic effects in pre-clinical and clinical studies, and combination checkpoint blockade with bacterial vaccine vectors have produced increased effector immune responses in pre-clinical models. The future of immune checkpoint blockade may be as a powerful adjuvant alongside the current standard of care.
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