PDF(Pubmed)
Abstract：
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.
摘要：
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,但在治疗T细胞恶性肿瘤方面仍有许多挑战，例如缺乏独特的肿瘤抗原，它们对T细胞扩增的限制，以及需要第三方捐赠者或基因组编辑。因此,我们需要寻找新的CART细胞治疗靶点来克服这些挑战.这里,我们发现,成人T细胞白血病/淋巴瘤(ATLL)患者和ATLL细胞的CCR8表达均增加,但不表达CD7.此外，在T细胞中靶向CCR8不会损害T细胞体外扩增.重要的是,抗CCR8CART细胞在体外和体内对ATLL-和其他表达CCR8的T-ALL细胞表现出抗肿瘤作用，并延长了ATLL和Jurkat荷瘤小鼠模型的生存期。总之,这些共同的结果表明,抗CCR8CART细胞具有很强的抗肿瘤活性,代表了ATLL和CCR8+肿瘤的一种有希望的治疗方法.
