The landscape of bispecific T cell engager in cancer treatment.
The landscape of bispecific T cell engager in cancer treatment.
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DOI：
10.1186/s40364-021-00294-9
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发表时间：
2021-05-26
影响因子：
11.1
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Zhou S;Liu M;Ren F;Meng X;Yu J
基于T细胞的免疫疗法已经彻底改变了各种癌症的治疗模式，然而，继发于肿瘤部位缺乏显著T细胞浸润的有限反应率仍然是一个主要问题。为了解决这一限制，正在深入研究用于重定向T细胞以治疗癌症的策略，而双特异性T细胞介导剂（BiTE）疗法构成了最有前途的治疗方法之一。BiTE是具有独特功能的双特异性抗体构建体，其同时结合肿瘤细胞上的抗原和T细胞上的表面分子以诱导肿瘤溶解。以blinatumomab为代表的BiTE疗法在治疗B细胞恶性肿瘤方面取得了令人瞩目的疗效。然而，对BiTE疗法的抗性的主要机制与抗原损失和免疫抑制因子（例如免疫检查点的上调）相关。因此，抗体构建体的修饰和寻找设计用于进一步增强治疗功效以及降低毒性的组合策略已成为紧迫的问题，特别是对于其中对BiTE疗法的响应总是较差的实体瘤。特别是，专注于先天免疫的免疫疗法已经吸引了越来越多的兴趣，并且已经通过接合先天细胞或先天样细胞显示出有希望的抗肿瘤活性，其可以单独使用或补充当前的疗法。在这篇综述中，我们描述了BiTE治疗的前景，包括潜在反应预测因子的临床进展，治疗毒性和耐药性的挑战，以及新型免疫细胞为基础的免疫治疗的发展。
T cell-based immunotherapies have revolutionized treatment paradigms in various cancers, however, limited response rates secondary to lack of significant T-cell infiltration in the tumor site remain a major problem. To address this limitation, strategies for redirecting T cells to treat cancer are being intensively investigated, while the bispecific T cell engager (BiTE) therapy constitutes one of the most promising therapeutic approaches. BiTE is a bispecific antibody construct with a unique function, simultaneously binding an antigen on tumor cells and a surface molecule on T cells to induce tumor lysis. BiTE therapy represented by blinatumomab has achieved impressive efficacy in the treatment of B cell malignancies. However, major mechanisms of resistance to BiTE therapy are associated with antigen loss and immunosuppressive factors such as the upregulation of immune checkpoints. Thus, modification of antibody constructs and searching for combination strategies designed to further enhance treatment efficacy as well as reduce toxicity has become an urgent issue, especially for solid tumors in which response to BiTE therapy is always poor. In particular, immunotherapies focusing on innate immunity have attracted increasing interest and have shown promising anti-tumor activity by engaging innate cells or innate-like cells, which can be used alone or complement current therapies. In this review, we depict the landscape of BiTE therapy, including clinical advances with potential response predictors, challenges of treatment toxicity and resistance, and developments of novel immune cell-based engager therapy.
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影响因子：
46.9
作者：
Choi, Bryan D.;Yu, Xiaoling;Maus, Marcela V.
通讯作者：
Maus, Marcela V.
影响因子：
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作者：
Assi, Rita;Kantarjian, Hagop;Jabbour, Elias
通讯作者：
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影响因子：
11.4
作者：
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通讯作者：
Bachmann, M.
影响因子：
20.3
作者：
Braig, Friederike;Brandt, Anna;Binder, Mascha
通讯作者：
Binder, Mascha
影响因子：
64.8
作者：
Alspach, Elise;Lussier, Danielle M.;Schreiber, Robert D.
通讯作者：
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