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Updated: Jun 5, 2026
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity
Julian Hübner1, Marah Alsalkini2, Rhonda McFleder3
1Chair of Cellular Immunotherapy, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Background:
While chimeric antigen receptor (CAR) T cells have achieved encouraging remission rates in hematological malignancies, they have demonstrated limited success in treating glioblastoma (GBM), particularly due to high intratumoral and intertumorous heterogeneity. In this study, we identified a consistently expressed target antigen, podoplanin (PDPN), and evaluated the potential of a PDPN-CAR T cell and GD2-CAR T cell blend to target heterogeneous GBM.
Methods:
Target antigen screening included clinical samples, cell lines and healthy tissues, as well as public RNA sequencing datasets. The anti-tumor function of CAR T cells was examined in co-culture experiments with GBM cell lines and patient-derived organoids (PDOs), and in vivo after locoregional delivery in orthotopic xenograft models.
Results:
CAR T cells demonstrated strong anti-tumor activity against several cell lines and PDOs from multiple patients. PDPN and GD2 were expressed in all PDOs, and regardless of the antigen expression pattern, the CAR T cell blend induced significantly higher apoptosis levels in organoids compared with single-antigen targeting CAR T cells. In vivo, we observed efficient tumor regression after locoregional administration of monospecific CAR T cells. While heterogeneous orthotopic tumors eventually relapsed in these groups, therapy with the CAR T cell blend significantly increased overall survival and even achieved a cure in the majority of mice.
Conclusion:
This novel PDPN/GD2 CAR T cell blend demonstrated robust efficacy in advanced preclinical GBM models, suggesting its potential to treat heterogeneous GBM and address limitations associated with single-antigen CAR T cell therapies.
Insights
A novel blend of chimeric antigen receptor (CAR) T cells targeting PDPN and GD2 shows promise for treating glioblastoma (GBM). This CAR T cell therapy effectively targets heterogeneous GBM tumors, improving survival rates in preclinical models.
Area of Science:
- Immunotherapy
- Oncology
- Cancer Research
Background:
- Chimeric antigen receptor (CAR) T cells show limited success in glioblastoma (GBM) due to tumor heterogeneity.
- Podoplanin (PDPN) identified as a consistently expressed target antigen in GBM.
- Investigated a PDPN-CAR T cell and GD2-CAR T cell blend for heterogeneous GBM treatment.
Purpose of the Study:
- Evaluate the efficacy of a dual-target (PDPN/GD2) CAR T cell blend against heterogeneous glioblastoma.
- Address limitations of single-antigen CAR T cell therapies in GBM treatment.
Main Methods:
- Screened target antigens using clinical samples, cell lines, healthy tissues, and RNA sequencing data.
- Assessed CAR T cell anti-tumor function in co-culture with GBM cell lines and patient-derived organoids (PDOs).
- Evaluated efficacy in vivo using locoregional delivery in orthotopic xenograft models.
Main Results:
- CAR T cells exhibited strong anti-tumor activity against GBM cell lines and PDOs.
- The PDPN/GD2 CAR T cell blend induced higher apoptosis in PDOs compared to single-target CAR T cells.
- In vivo, the blend significantly increased overall survival and achieved cures in a majority of mice with heterogeneous orthotopic tumors.
Conclusions:
- The novel PDPN/GD2 CAR T cell blend demonstrated significant efficacy in preclinical GBM models.
- This dual-targeting approach shows potential for treating heterogeneous GBM.
- The CAR T cell blend may overcome limitations of single-antigen therapies in GBM.
