肿瘤细胞治疗研究
英文原题：Sensitive CAR T cells redefine targetable CD70 expression in solid tumors.
Sensitive CAR T cells redefine targetable CD70 expression in solid tumors.
实体瘤抗原异质性是包括嵌合抗原受体（CAR）T细胞在内的癌症免疫治疗面临的一大挑战。
实体瘤抗原异质性是包括嵌合抗原受体（CAR）T细胞在内的癌症免疫治疗面临的主要挑战。与B细胞恶性肿瘤的CD19不同，尚未鉴定出在实体瘤中泛细胞表达且在正常重要细胞中缺失的靶点。CD70是一个有前景的候选靶点，其在生理上局限于免疫细胞亚群，并在多种癌症中异常表达。我们发现肿瘤中异质性的CD70表达受表观遗传调控，在单个细胞中从高到极低不等，用常规检测方法可能显示为阴性。使用一种高灵敏度的CD70受体，即共表达CD80和4-1BBL用于共刺激的HLA非依赖性T细胞（HIT）受体，我们有效清除了逃避原型CAR T细胞的CD70异质性肿瘤。这些发现为治疗多种实体瘤提供了一种潜在策略。
Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.
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