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癌症免疫治疗中的 T 细胞重定向双特异性抗体:最新进展。

T cell-redirecting bispecific antibodies in cancer immunotherapy: recent advances.

机构信息

Key Laboratory of Biorheological Science and Technology (Ministry of Education), College of Bioengineering, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing, 400044, China.

出版信息

J Cancer Res Clin Oncol. 2019 Apr;145(4):941-956. doi: 10.1007/s00432-019-02867-6. Epub 2019 Feb 23.

Abstract

PURPOSE

Globally, cancer is a critical illness which seriously threatens human health. T-cell-based cancer immunotherapy for some patients has demonstrated impressive achievements including chimeric antigen receptor T cells, immune checkpoint inhibitors and T cell-redirecting bispecific antibodies (TRBAs). TRBAs recruit T cells to lyse cancer cells bypassing the antigen presentation through the major histocompatibility complex pathways. In this review we summarized the TRBAs formats, biophysical characteristics, the preclinical and clinical trial results, as well as the challenges faced by TRBAs in tumour therapy.

METHODS

Herein the relevant literature and clinical trials from the PubMed and ClinicalTrials.gov database.

RESULTS

The advances in protein engineering technology have generated diverse TRBAs format which can be classified into two categories: IgG-like TRBAs and non-IgG-like TRBAs. Multiple applications of TRBAs showed encouraging curative effect and entered clinical trials for lymphoid malignancy and solid tumour.

CONCLUSIONS

TRBA is a powerful tool for the cancer treatment and the clinical studies showed potent anti-tumour efficacy in hematologic malignancies. Although the clinical outcomes of TRBAs in solid tumours are less satisfied than hematologic malignancies, many preclinical antibodies and combination therapies are being evaluated.

摘要

目的

在全球范围内,癌症是一种严重威胁人类健康的重大疾病。对于某些患者,基于 T 细胞的癌症免疫疗法已经取得了令人瞩目的成就,包括嵌合抗原受体 T 细胞、免疫检查点抑制剂和 T 细胞重定向双特异性抗体(TRBAs)。TRBAs 通过主要组织相容性复合物途径绕过抗原呈递,招募 T 细胞裂解癌细胞。在本综述中,我们总结了 TRBAs 的形式、生物物理特性、临床前和临床试验结果,以及 TRBAs 在肿瘤治疗中面临的挑战。

方法

本文检索了 PubMed 和 ClinicalTrials.gov 数据库中的相关文献和临床试验。

结果

蛋白质工程技术的进步产生了多种 TRBAs 形式,可分为两类:IgG 样 TRBAs 和非 IgG 样 TRBAs。TRBAs 的多种应用显示出令人鼓舞的疗效,并进入了淋巴恶性肿瘤和实体瘤的临床试验。

结论

TRBA 是癌症治疗的有力工具,临床研究显示在血液恶性肿瘤中具有强大的抗肿瘤疗效。尽管 TRBAs 在实体瘤中的临床疗效不如血液恶性肿瘤,但许多临床前抗体和联合疗法正在评估中。

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