China-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 May 26;13:808347. doi: 10.3389/fimmu.2022.808347. eCollection 2022.
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 . Importantly, anti-CCR8 CAR T cells exhibited antitumor effects on ATLL- and other CCR8-expressing T-ALL cells and , 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.
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，但在用于治疗 T 细胞恶性肿瘤时仍面临许多挑战，例如缺乏独特的肿瘤抗原、T 细胞扩增受限以及需要第三方供体或基因组编辑。因此，我们需要为 CAR T 细胞治疗寻找新的靶点，以克服这些挑战。在这里，我们发现成人 T 细胞白血病/淋巴瘤 (ATLL) 患者和 ATLL 细胞均表达增加的 CCR8，但不表达 CD7。此外，靶向 T 细胞中的 CCR8 不会损害 T 细胞的扩增。重要的是，抗 CCR8 CAR T 细胞对 ATLL 和其他表达 CCR8 的 T-ALL 细胞具有抗肿瘤作用，并且延长了 ATLL 和 Jurkat 肿瘤荷瘤小鼠模型的存活时间。总之，这些结果表明，抗 CCR8 CAR T 细胞具有强大的抗肿瘤活性，是治疗 ATLL 和 CCR8 肿瘤的一种很有前途的治疗方法。
