期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 70, 期 7, 页码 2059-2071出版社
SPRINGER
DOI: 10.1007/s00262-020-02838-8
关键词
Trop2; CAR; Solid tumor; CD27
资金
- Science and Technology Department of Guangdong Province [2017A050501010, 2016A050503023]
- Guangzhou Science, Technology and Innovation Commission [201807010042]
Chimeric antigen receptor (CAR) T cell therapy has been successful in treating lymphoma malignancies but less so in treating solid tumors. A study developed a CAR targeting Trop2 (T2-CAR) with different co-stimulatory intercellular domains and found that CD27-based T2-CAR T cells demonstrated higher antitumor activity in tumor-bearing mouse models. Additionally, CD27-based T2-CAR T cells were found to upregulate IL-7R alpha expression and downregulate PD-1 expression. These findings suggest that a CD27-based T2-CAR T cell approach may be suitable for clinical applications.
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-7R alpha 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.
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