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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
Targeting CDH17 with Chimeric Antigen Receptor-Redirected T Cells in Small Cell Lung Cancer
Wen Tian1, Jinhui Zhao2, Wenzhong Wang3
1Second Department of Oncology, Cangzhou Central Hospital, NO.16 Xinhua West Road, Cangzhou, 061000, Hebei, China. Tianwencz2015@163.com.
Background:
Chimeric antigen receptor T cell (CAR-T) therapy stands as a precise and targeted approach in the treatment of malignancies. In this study, we investigated the feasibility of targeting Cadherin 17 (CDH17) with CDH17 CAR-T cells as a therapeutic modality for small cell lung cancer (SCLC).
Methods:
CDH17 expression levels were assessed in human SCLC tumor tissues and cell lines using qPCR and Western blot. Subsequently, we established CDH17 CAR-T cells and assessed their cytotoxicity by co-culturing them with various SCLC cell lines at different effector-to-target (E:T) ratios, complemented by ELISA assays. To ascertain the specificity of CDH17 CAR-T cells, we conducted experiments on SCLC cells with and without CDH17 expression (shRNAs). Furthermore, we employed an SCLC xenograft model to evaluate the in vivo efficacy of CDH17 CAR-T cells.
Results:
Our results revealed a significant upregulation of CDH17 in both SCLC tissues and cell lines. CDH17 CAR-T cells exhibited robust cytotoxic activity against SCLC cells in vitro, while demonstrating no cytotoxicity towards CDH17-deficient SCLC cells and HEK293 cells that lack CDH17 expression. Importantly, the production of IFN-γ and TNF-α by CDH17 CAR-T cells correlated with their cytotoxic potency. Additionally, treatment with CDH17 CAR-T cells significantly decelerated the growth rate of SCLC-derived xenograft tumors in vivo. Remarkably, no significant difference in body weight was observed between the control group and the group treated with CDH17 CAR-T cells.
Conclusions:
The preclinical data open further venues for the clinical use of CDH17 CAR-T cells as an immunotherapeutic strategy for SCLC treatment.
Insights
Chimeric antigen receptor T cell (CAR-T) therapy targeting Cadherin 17 (CDH17) shows promise for small cell lung cancer (SCLC). CDH17 CAR-T cells effectively reduced SCLC tumor growth in preclinical models.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor T cell (CAR-T) therapy offers targeted cancer treatment.
- Small cell lung cancer (SCLC) remains a challenging malignancy to treat effectively.
Purpose of the Study:
- To investigate the potential of targeting Cadherin 17 (CDH17) using CDH17 CAR-T cells for SCLC treatment.
- To evaluate the efficacy and specificity of CDH17 CAR-T cells against SCLC.
Main Methods:
- Assessed CDH17 expression in SCLC tissues and cell lines via qPCR and Western blot.
- Developed and tested CDH17 CAR-T cell cytotoxicity in vitro against SCLC cell lines.
- Evaluated in vivo efficacy using an SCLC xenograft mouse model.
Main Results:
- CDH17 was significantly upregulated in SCLC tissues and cell lines.
- CDH17 CAR-T cells demonstrated potent in vitro cytotoxicity against CDH17-expressing SCLC cells, with no effect on CDH17-deficient cells.
- In vivo studies showed CDH17 CAR-T cell treatment significantly inhibited SCLC xenograft tumor growth without adverse effects on body weight.
Conclusions:
- Preclinical findings support CDH17 CAR-T cell therapy as a viable immunotherapeutic strategy for SCLC.
- Further clinical investigation of CDH17 CAR-T cells for SCLC is warranted.
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