Zhang Gui-Zhen, Li Tian-Fang, Han Shuang-Yin
Key Laboratory of Kidney Disease Immunization in Henan Province, People's Hospital of Zhengzhou University, Zhengzhou, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Arch Med Sci. 2019 May 8;17(5):1213-1220. doi: 10.5114/aoms.2019.84888. eCollection 2021.
Significant progresses have been made in adoptive cell therapy with CAR-T cells for cancers, especially for hematological malignancies. However, the treatment of solid tumors still poses a tremendous challenge and remains an unmet medical need. Several factors are held responsible for the inadequate responses: tumor heterogeneity, inefficient homing of T cells to tumor tissues, immunosuppressive microenvironment and the shortage of specific antigens shortage. Mesothelin is a cell-surface glycoprotein highly expressed in many types of solid tumors. As such, it has attracted much attention as a molecular target in cancer immunotherapy. Here, we delineate the barriers imposed by solid tumors on CARs, outline the rationale of mesothelin as a target for immunotherapy, summarize the preclinical and clinical results of mesothelin-targeted therapies, and extrapolate the expected results of CAR-T cells directed against mesothelin for solid tumors.
嵌合抗原受体（CAR）-T细胞过继性细胞疗法在癌症治疗，尤其是血液系统恶性肿瘤治疗方面取得了重大进展。然而，实体瘤的治疗仍然面临巨大挑战，仍是未被满足的医疗需求。多种因素导致了疗效不佳：肿瘤异质性、T细胞向肿瘤组织归巢效率低下、免疫抑制微环境以及特异性抗原短缺。间皮素是一种在多种实体瘤中高度表达的细胞表面糖蛋白。因此，它作为癌症免疫治疗的分子靶点备受关注。在此，我们阐述实体瘤对CAR造成的障碍，概述间皮素作为免疫治疗靶点的理论依据，总结间皮素靶向治疗的临床前和临床结果，并推断针对实体瘤的间皮素靶向CAR-T细胞的预期结果。
