近日，美国哥伦比亚大学Michel Sadelain及其团队的研究发现敏感的CAR-T细胞重新定义了实体瘤中CD70的靶向表达。这一研究成果于2026年2月26日发表在国际顶尖学术期刊《科学》上。

研究小组发现肿瘤中CD70的异质表达受表观遗传调控，在单个细胞中从高到极低，通过常规检测方法呈现阴性。使用高度敏感的CD70受体，HLA-非依赖性T细胞（HIT）受体共表达CD80和4-1BBL进行共刺激，该团队有效地消除了逃避原型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的策略。

据介绍，实体肿瘤抗原异质性是癌症免疫治疗的主要挑战，包括嵌合抗原受体（CAR） T细胞。与B细胞恶性肿瘤的CD19不同，没有发现在实体瘤中泛细胞表达而在正常生命细胞中缺失的靶标。CD70是一个很有前途的候选者，生理上局限于免疫细胞亚群，在许多癌症中异常表达。

附：英文原文

Title: Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

Author: Sophie A. Hanina, Tyler Park, Michael Lopez, Vinagolu K. Rajasekhar, Jorge Mansilla-Soto, Sascha Haubner, Huiyong Zhao, Friederike Kogel, Sarah Nataraj, Priyam Banerjee, Richard Koche, Pierre-Jacques Hamard, Zeynep C. Tarcan, Dennis S. Chi, Dmitriy Zamarin, John H. Healey, Elisa de Stanchina, Robert J. Motzer, Ritesh R. Kotecha, A. Ari Hakimi, Christina S. Leslie, Michel Sadelain

Issue&Volume: 2026-02-26

Abstract: 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.

DOI: adv7378

Source: https://www.science.org/doi/10.1126/science.adv7378