肿瘤细胞治疗研究
英文原题：The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies.
这些综合结果表明，抗 CCR8 CAR T 细胞具有强效抗肿瘤活性，是治疗 ATLL 和 CCR8⁺ 肿瘤的一种有前景的治疗方法。
嵌合抗原受体（CAR）T 细胞已成功用于治疗 B 细胞白血病和淋巴瘤，但治疗 T 细胞恶性肿瘤仍面临诸多挑战，例如缺乏独特肿瘤抗原、T 细胞扩增受限，以及需要第三方供者或进行基因组编辑。因此，需要寻找新的 CAR T 细胞治疗靶点以克服这些挑战。我们发现，成人 T 细胞白血病/淋巴瘤（ATLL）患者及 ATLL 细胞均表达较高水平 CCR8，但不表达 CD7。此外，在 T 细胞中靶向 CCR8 不会损害体外 T 细胞扩增。重要的是，抗 CCR8 CAR T 细胞在体内外均对 ATLL 和其他表达 CCR8 的 T-ALL 细胞产生抗肿瘤效应，并延长 ATLL 和 Jurkat 肿瘤荷瘤小鼠模型的生存期。综上，抗 CCR8 CAR T 细胞具有强效抗肿瘤活性，是治疗 ATLL 和 CCR8⁺ 肿瘤的有前景策略。
Chimeric antigen receptor (CAR) T cells have been successfully used in the therapy of B cell leukemia and lymphoma, but still have many challenges in their use for treating T cell malignancies, such as the lack of unique tumor antigens, their limitation of T cell expansion, and the need for third party donors or genome editing. Therefore, we need to find novel targets for CAR T cell therapy to overcome these challenges. Here, we found that both adult T-cell leukemia/lymphoma (ATLL) patients and ATLL cells had increased CCR8 expression but did not express CD7. Moreover, targeting CCR8 in T cells did not impair T cell expansion in vitro . Importantly, anti-CCR8 CAR T cells exhibited antitumor effects on ATLL- and other CCR8-expressing T-ALL cells in vitro and in vivo , and prolonged the survival of ATLL and Jurkat tumor-bearing mouse models. In conclusion, these collective results show that anti-CCR8 CAR T cells possess strong antitumor activity and represent a promising therapeutic approach for ATLL and CCR8 + tumors.
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