CD27 enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors

• Published in: Cancer Immunology, Immunotherapy Vol. 70; no. 7; pp. 2059 - 2071
• Main Authors: Chen, Huanpeng, Wei, Fengjiao, Yin, Meng, Zhao, Qingyu, Liu, Zhonghua, Yu, Bolan, Huang, Zhaofeng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2021; Springer Nature B.V
• Subjects: Animal models; Animals; Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Antitumor activity; Apoptosis; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer Research; CD27 antigen; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Proliferation; Cell surface; Cell therapy; Chimeric antigen receptors; Effector cells; Female; Humans; Immunology; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Lymphoma; Medicine; Medicine & Public Health; Metastases; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Oncology; Original; Original Article; PD-1 protein; Receptors, Chimeric Antigen - immunology; Solid tumors; Tumor Cells, Cultured; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism; Tumors; Xenograft Model Antitumor Assays; Solid tumor; CD27; CAR; Trop2
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-020-02838-8

Chimeric antigen receptor (CAR) T cell therapy, a type of adoptive cell therapy, has been successfully used when treating lymphoma malignancies, but not nearly as successful in treating solid tumors. Trophoblast cell surface antigen 2 (Trop2) is expressed in various solid tumors and plays a role in tumor growth, invasion, and metastasis. In this study, a CAR targeting Trop2 (T2-CAR) was developed with different co-stimulatory intercellular domains. T2-CAR T cells demonstrated a powerful killing ability in the presence of Trop2-positive cells following an in vitro assay. Moreover, T2-CAR T cells produced multiple effector cytokines under antigen stimulation. In tumor-bearing mouse models, the CD27-based T2-CAR T cells showed a higher antitumor activity. Additionally, more CD27-based T2-CAR T cells survived in tumor-bearing mice spleens as well as in the tumor tissue. CD27-based T2-CAR T cells were also found to upregulate IL-7Rα expression, while downregulating PD-1 expression. In conclusion, the CD27 intercellular domain can enhance the T2-CAR T cell killing effect via multiple mechanisms, thus indicating that a CD27-based T2-CAR T cell approach is suitable for clinical applications.