表达 CAR 的 T 细胞，其胞外域带有 BTLA，可有效对抗 HVEM 过表达的黑色素瘤细胞系。

T Cells Expressing CAR Equipped With Extracellular Domain of BTLA Are Effective Against HVEM-over-expressing Melanoma Cell Lines.

机构信息

Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.

Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, Daejeon, Republic of Korea.

出版信息

Anticancer Res. 2023 Aug;43(8):3419-3427. doi: 10.21873/anticanres.16517.

DOI:10.21873/anticanres.16517

PMID:37500142

Abstract

BACKGROUND/AIM: Several chimeric antigen receptor (CAR) T cells have been used to treat melanoma but have not shown favorable results. This study investigated whether Herpes virus entry mediator (HVEM), which is overexpressed in melanoma, is a potential novel antigen for CAR T cell therapy.

MATERIALS AND METHODS

A CAR construct, composed of the BTLA extracellular domain for HVEM recognition (BTLA-28z), was developed and tested.

RESULTS

Jurkat cells transduced with BTLA-28z exhibited enhanced IL-2 secretion when incubated with HVEM-over-expressing melanoma cells. KHYG-1 cells transduced with BTLA-28z also lysed melanoma cell lines. Using primary T cells, we generated CAR T cells targeting HVEM. BTLA-28z CAR T cells exhibited excellent lytic activities against melanoma cell lines.

CONCLUSION

HVEM-targeting CAR T cells may be useful for the treatment of melanoma.

摘要

背景/目的：已经有几种嵌合抗原受体（CAR）T 细胞被用于治疗黑色素瘤，但并未显示出良好的效果。本研究旨在探讨在黑色素瘤中过表达的疱疹病毒进入介体（HVEM）是否是 CAR T 细胞治疗的潜在新型抗原。

材料和方法

开发并测试了一种由 HVEM 识别的 BTLA 细胞外结构域（BTLA-28z）组成的 CAR 构建体。

结果

与过表达 HVEM 的黑色素瘤细胞孵育时，转导了 BTLA-28z 的 Jurkat 细胞表现出增强的 IL-2 分泌。转导了 BTLA-28z 的 KHYG-1 细胞也能溶解黑色素瘤细胞系。使用原代 T 细胞，我们生成了靶向 HVEM 的 CAR T 细胞。BTLA-28z CAR T 细胞对黑色素瘤细胞系表现出优异的溶解活性。