溶瘤病毒
医学
Blinatumoab公司
细胞毒性T细胞
免疫学
人口
免疫系统
T细胞
免疫疗法
抗原
癌症研究
癌症
免疫检查点
生物
内科学
体外
CD19
生物化学
环境卫生
作者
Winston M Zhu,Mark R. Middleton
标识
DOI:10.1093/immadv/ltad013
摘要
Summary Bispecific T-cell engagers (BiTEs) redirect endogenous T-cell populations to cells expressing tumour-associated antigens to induce tumour cell killing. This inherently relies upon a cytotoxic T-cell population that is able to be recruited. In many cancers, immune checkpoints and other immunosuppressive factors in the tumour microenvironment lead to a population of anergic T-cells which cannot be redirected to tumour killing and thus impede the efficacy of BiTE therapy. Furthermore, there is evidence that BiTE therapy itself can increase immune checkpoint expression, and this is thought to be a major escape mechanism for the BiTE therapy blinatumomab. To overcome these inadequate T-cell responses, BiTEs may be combined with checkpoint inhibitors, chemotherapy, costimulatory molecules or oncolytic viruses. Study of these combinations is needed to expand the use of BiTEs in solid malignancies. This review covers the rationale, preclinical evidence and any clinical trials for these combination therapies and a few other less-studied combinations.
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