Navigating CAR-T cells through the solid-tumour microenvironment

被引：348

作者：

Hou, Andrew J. ^{[1
]}

Chen, Laurence C. ^{[1
]}

Chen, Yvonne Y. ^{[1
,2
,3
]}

机构：

[1] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Parker Inst Canc Immunotherapy Ctr, Los Angeles, CA 90095 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2021年 / 20卷 / 07期

基金：

美国国家科学基金会;

关键词：

CHIMERIC ANTIGEN RECEPTORS; FIBROBLAST ACTIVATION PROTEIN; ANTITUMOR EFFICACY; EFFECTOR FUNCTION; CHECKPOINT BLOCKADE; CANCER REGRESSION; DONOR LYMPHOCYTES; NORMAL-TISSUES; HOST IMMUNITY; SUICIDE-GENE;

D O I：

10.1038/s41573-021-00189-2

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Chimeric antigen receptors (CARs) have shown limited efficacy in the treatment of solid tumours. In this Review, Chen and colleagues discuss various engineering strategies to overcome the obstacles that the tumour microenvironment poses to CAR-T cells, to produce next-generation T cells with enhanced specificity and sustained function for the treatment of solid tumours. The adoptive transfer of T cells that are engineered to express chimeric antigen receptors (CARs) has shown remarkable success in treating B cell malignancies but only limited efficacy against other cancer types, especially solid tumours. Compared with haematological diseases, solid tumours present a unique set of challenges, including a lack of robustly expressed, tumour-exclusive antigen targets as well as highly immunosuppressive and metabolically challenging tumour microenvironments that limit treatment safety and efficacy. Here, we review protein- and cell-engineering strategies that seek to overcome these obstacles and produce next-generation T cells with enhanced tumour specificity and sustained effector function for the treatment of solid malignancies.

引用

页码：531 / 550

页数：20

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