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Poster Presentations
12. Young researchers session
P12.10 In vivo dynamics and anti-tumor effects of B7-H3-directed CAR T-cells in an orthotopic medulloblastoma mouse model
  1. JJ Herold1,
  2. N Teske1,
  3. NN Kutlu2,
  4. L Dengler1,
  5. C Eberle1,
  6. E Nikolaishvili1,
  7. P Karschnia1,
  8. J Blobner1,
  9. K Müller3,
  10. S Langer3,
  11. V Buschinger4,
  12. L Warmuth4,
  13. DH Busch4,
  14. VR Buchholz4,
  15. N Thon1,
  16. JC Tonn1,
  17. T Feuchtinger2 and
  18. L von Baumgarten3,1
  1. 1Department of Neurosurgery, University Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany, München, Germany
  2. 2Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation Dr. von Hauner Children’s Hospital, University Hospital of the Ludwig- Maximilians-University Munich, Munich, Germany, München, Germany
  3. 3Department of Neurology, University Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany, München, Germany
  4. 4Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitaet Muenchen (TUM), Munich, Germany, München, Germany

Abstract

Background The majority of solid tumors in pediatric patients occurs in the central nervous system, with medulloblastoma accounting for approximately 20% of pediatric brain tumors. Current treatment, involving resection, radiotherapy, and chemotherapy, improves long-term survival but is associated with significant adverse effects. Hence, there is an urgent need for novel therapeutic approaches. Chimeric Antigen Receptor (CAR) T-cell therapy has shown promise in treating hematologic malignancies. Its potential suitability for medulloblastoma remains uncertain. Initial preclinical and clinical studies suggest efficacy, but the dynamics of CAR-T recruitment, their interactions with tumor cells, optimal administration routes (intravenous, intraventricular, intratumoral), and mechanisms of potential treatment failure are unclear. To address these gaps, we aimed to establish an in vivo model for further investigation of CAR T-treatment in medulloblastoma.

Materials and Methods Three weeks after the microsurgical implantation of a chronic cerebellar window in immunodeficient FoxN1 mice, red fluorescent human medulloblastoma cells (DAOYtdt; SHH) were injected into the cerebellum. After 20 days solid tumor had formed, and CAR T-cellsGFP directed against the surface antigen B7-H3 were injected at a distance of 1mm adjacent to the tumor. As control, we used antiCD-19 CAR T-cellsGFP. Intravital two-photon laser scanning microscopy was used to longitudinally monitor tumor growth and CAR T-cells at a cellular level.

Results We successfully established a xenogeneic orthotopic medulloblastoma model which allows repetitive in vivo microscopy on a cellular resolution. Our preliminary results show, that following intracranial injection CAR T-cells were recruited to the tumor site and reduced tumor growth.

Conclusions Our mouse model can be used to evaluate the efficacy of CAR T-treatment for medulloblastoma and analyze CAR T-biology at a cellular level. Preliminary data showed a possible efficacy of antiB7-H3 CARs. In further experiments, we plan to dissect the efficacy of different application routes on the treatment efficacy.

J.J. Herold: None. N. Teske: None. N.N. Kutlu: None. L. Dengler: None. C. Eberle: None. E. Nikolaishvili: None. P. Karschnia: None. J. Blobner: None. K. Müller: None. S. Langer: None. V. Buschinger: None. L. Warmuth: None. D.H. Busch: None. V.R. Buchholz: None. N. Thon: None. J.C. Tonn: None. T. Feuchtinger: None. L. von Baumgarten: None.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2024-ITOC10.64

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