Driving CARs on the uneven road of antigen heterogeneity in solid tumors

被引：89

作者：

Chen, Nan ^{[1
]}

Li, Xiaoyu ^{[1
]}

Chintala, Navin K. ^{[1
]}

Tano, Zachary E. ^{[1
]}

Adusumilli, Prasad S. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, 1275 York Ave, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, 1275 York Ave, New York, NY 10065 USA

来源：

CURRENT OPINION IN IMMUNOLOGY | 2018年 / 51卷

基金：

美国国家卫生研究院;

关键词：

CELL LUNG-CANCER; ENGINEERED T-CELLS; PANCREATIC-CANCER; IMMUNE MICROENVIRONMENT; ANTITUMOR-ACTIVITY; TARGET ANTIGEN; EXPRESSION; RECEPTORS; ADENOCARCINOMA; MESOTHELIN;

D O I：

10.1016/j.coi.2018.03.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.

引用

页码：103 / 110

页数：8

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