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Updated: Nov 10, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Development of Antigen-specific Chimeric Antigen Receptor KHYG-1 Cells for Glioblastoma
Chung Hyo Kang1, Yeongrin Kim1,2, So Myoung Lee1
1Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
Background/Aim:
Glioblastoma is the most common cancer among primary brain tumors, however, its prognosis and treatment advances are very poor. Here, we investigated whether c-Met, FOLR1, and AXL proteins are promising targets for chimeric antigen receptor (CAR) T-cell therapy, for they are known to be over-expressed in a variety of solid tumors.
Materials And Methods:
CAR constructs were prepared and CAR KHYG-1 cells targeting c-Met, FOLR1, or AXL were made by lentiviral transduction. The activity of CAR KHYG-1 cells against cancer cells was measured by cytokine secretion and cell lysis assays.
Results:
c-Met and AXL were over-expressed in most glioblastoma cell lines (11/13), but not in neuroblastoma cell lines (0/8). FOLR1 was over-expressed only in one among 16 glioblastoma cell lines. Our antigen-specific CAR KHYG-1 cells eradicated target positive glioblastoma cells selectively.
Conclusion:
Anti-c-Met and anti-AXL CAR NK or T cells could be effective in glioblastoma cells.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for glioblastoma treatment. Targeting c-Met and AXL proteins effectively eradicated glioblastoma cells in vitro, suggesting potential therapeutic applications.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Glioblastoma is an aggressive primary brain tumor with limited treatment options.
- Chimeric antigen receptor (CAR) T-cell therapy is an emerging cancer treatment strategy.
- Identifying suitable tumor-specific targets is crucial for CAR T-cell therapy efficacy.
Purpose of the Study:
- To evaluate c-Met, FOLR1, and AXL as potential targets for CAR T-cell therapy in glioblastoma.
- To assess the expression levels of c-Met, FOLR1, and AXL in glioblastoma cell lines.
- To determine the efficacy of CAR-engineered KHYG-1 cells against glioblastoma cells expressing these targets.
Main Methods:
- CAR constructs targeting c-Met, FOLR1, or AXL were developed.
- CAR KHYG-1 cells were generated using lentiviral transduction.
- Cytokine secretion and cell lysis assays were performed to measure CAR KHYG-1 cell activity against cancer cells.
Main Results:
- c-Met and AXL were over-expressed in 11 out of 13 glioblastoma cell lines, but not in neuroblastoma cell lines.
- FOLR1 was over-expressed in only 1 out of 16 glioblastoma cell lines.
- Antigen-specific CAR KHYG-1 cells demonstrated selective eradication of glioblastoma cells expressing the targeted antigens.
Conclusions:
- Anti-c-Met and anti-AXL CAR NK or T cells hold potential for treating glioblastoma.
- c-Met and AXL are promising targets for developing CAR T-cell therapies for glioblastoma.
- Further research into CAR T-cell therapy targeting c-Met and AXL is warranted for glioblastoma treatment.
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