Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity

Hübner J, Alsalkini M, McFleder R, Toppeta F, Wagner J, Liguori R, Grams B, Meyer-Hofmann M, Diener L, Monoranu CM, Hagemann C, Ferrazzi F, Ip CW, Ernestus RI, Einsele H, Hudecek M, Löhr M, Nerreter T, Nickl V (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Journal for ImmunoTherapy of Cancer BioMed Central

Book Volume: 14

Journal Issue: 6

DOI: 10.1136/jitc-2025-014693

Abstract

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.

Authors with CRIS profile

Renato Liguori Sonderforschungsbereich/Transregio 305/1 Über die Analyse der metastatischen Koloniebildung zu neuen systemischen Krebstherapien Fulvia Ferrazzi Department of Nephropathology

Involved external institutions

Universitätsklinikum Würzburg DE Germany (DE) Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE)

How to cite

APA:

Hübner, J., Alsalkini, M., McFleder, R., Toppeta, F., Wagner, J., Liguori, R.,... Nickl, V. (2026). Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity. Journal for ImmunoTherapy of Cancer, 14(6). https://doi.org/10.1136/jitc-2025-014693

MLA:

Hübner, Julian, et al. "Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity." Journal for ImmunoTherapy of Cancer 14.6 (2026).

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