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Archive > Volume 33 Issue 6 > 2026,33(6):661-669. DOI:10.3872/j.issn.1007-385X.2026.06.008 Prev Next
Basic Research
Enhancing anti-glioblastoma efficacy of FAP-CTLA-4 CAR-T cells combined with apatinib and the underlying mechanisms
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Abstract:
[Abstract] Objective: To evaluate the anti-tumor efficacy of FAP-CTLA-4 CAR-T cells targeting fibroblast activation protein (FAP) and secreting anti-CTLA-4 single-chain antibody (scFv) combined with apatinib in the treatment of glioblastoma (GBM), and to explore the underlying mechanisms. Methods: A FAP-CTLA-4 CAR overexpression vector was constructed and transduced into T cells to generate FAP-CTLA-4 CAR-T cells. In vitro functions of CAR-T cells were evaluated by flow cytometry (CD69 expression) and ELISPOT assay (IFN-γ secretion). Proliferation assays were used to assess the proliferation capacity of FAP-CTLA-4 CAR-T cells, and cytotoxicity assays were performed to evaluate the anti-tumor effect of the combination treatment with apatinib on U-87 MG cells. A mouse U-87 MG xenograft tumor model was established, and tumor-bearing mice were assigned to the monotherapy group (FAP- CTLA-4 CAR-T or apatinib alone) and the combination therapy group (FAP-CTLA-4 CAR-T plus apatinib). Tumor growth was monitored; tumor tissue Ki-67/CD31 expression was detected by immunohistochemistry and immunofluorescence; apoptosis was assessed by TUNEL staining. In vivo CAR-T persistence was analyzed by flow cytometry; treatment safety was assessed via H-E staining and serum biochemistry. Results: Compared with the monotherapy group, the combination therapy group showed significantly · · 661 [[PAGE_INDEX=12 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) increased CAR-T cell activation, enhanced proliferation capacity, a higher proportion of IFN-γ-secreting cells and superior cytotoxicity against target cells (P < 0.05 or P < 0.01).In the xenograft mouse model, the combination therapy markedly suppressed tumor growth and prolonged survival (P < 0.05 or P < 0.01), inhibited tumor cell proliferation and microvessel density, promoted tumor cell apoptosis, and extended the survival of CAR-T cells within tumor tissues (P < 0.05 or P < 0.01), without causing toxic damage to major organs. Conclusion: The combination of FAP-CTLA-4 CAR-T cells and apatinib exhibits synergistic anti-tumor effects in GBM, enhancing therapeutic efficacy while maintaining safety, and may represent a promising novel strategy for the treatment of this disease.
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