Recently, B7-H3 was frequently reported to be overexpressed in various cancer types and has been suggested to be a promising target for cancer immunotherapy. In the present study, we analyzed the mRNA expression of B7-H3 in The Cancer Genome Atlas (TCGA) database and validated its expression across multiple cancer types. We then generated a novel B7-H3-targeted chimeric antigen receptor (CAR) and tested its antitumor activity both in vitro and in vivo. The B7-H3 expression heterogeneity and variation were frequent. Moderate or even high expression levels of B7-H3 were also observed in some tumor-adjacent tissues, but the staining intensity was weaker than that in tumor tissues. B7-H3 expression was absent or very low in normal tissues and organs. Flow cytometry indicated that the mean expression level of B7-H3 in eight bone marrow specimens from patients with acute myeloid leukemia (AML) was 57.2% (range 38.8–80.4). Furthermore, we showed that the B7-H3-targeted CAR-T cells exhibited significant antitumor activity against AML and melanoma in vitro and in xenograft mouse models. In conclusion, although B7-H3 represents a promising pan-cancer target, and B7-H3-redirected CAR-T cells can effectively control tumor growth, the expression heterogeneity and variation have to be carefully considered in translating B7-H3-targeted CAR-T cell therapy into clinical practice.

最近，经常报道B7-H3在各种类型的癌症中均过表达，并被认为是癌症免疫疗法的有希望的靶标。在本研究中，我们分析了癌症基因组图谱（TCGA）数据库中B7-H3的mRNA表达，并验证了其在多种癌症类型中的表达。然后，我们生成了靶向B7-H3的新型嵌合抗原受体（CAR），并在体外和体内测试了其抗肿瘤活性。B7-H3表达异质性和变异频繁。在一些邻近肿瘤的组织中也观察到中等或什至高水平的B7-H3表达，但是染色强度比在肿瘤组织中弱。在正常组织和器官中，B7-H3表达不存在或非常低。流式细胞仪显示，来自急性髓性白血病（AML）患者的八份骨髓标本中B7-H3的平均表达水平为57.2％（范围38.8–80.4）。此外，我们表明靶向B7-H3的CAR-T细胞在体外对AML和黑素瘤表现出显着的抗肿瘤活性和异种移植小鼠模型中。总之，尽管B7-H3代表了有希望的泛癌靶标，并且B7-H3重定向的CAR-T细胞可以有效地控制肿瘤的生长，但是在翻译靶向B7-H3的CAR-T时必须仔细考虑表达异质性和变异性T细胞疗法进入临床实践。