The Evaluation of Novel Targets for CAR T Therapy in Glioblastoma

Alker, Riza, Abel, Peter orcid iconORCID: 0000-0002-5221-7653, Griffiths, David Michael and Akhavan, David (2022) The Evaluation of Novel Targets for CAR T Therapy in Glioblastoma. Neuro-Oncology, 24 (4). iv22-iv23. ISSN 1522-8517

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The basis of this research revolves around the issue of limited expression of targetable tumour-specific antigens, heterogeneity, and mutation, which impede the development and success of CAR T therapy for glioblastoma. The research will identify an off-tumour cell target involved in tumour angiogenesis. The principal aim is to generate an off-tumour targeted CAR T and test their efficacy and safety in cell culture and animal models.

Analyse the prevalence and distribution of the target molecules via immunohistochemistry (IHC). Confirm IHC results via mRNA extraction. Analyse the target molecule’s serum concentrations via the Luminex instrument. Generate the off-tumour targeted CAR T using lentivirus. Assess tumour burden and progression via a bioluminescent imaging system. Assess toxicity in vitro against human pericytes and in vivo by monitoring mouse weight and submitting histologic tissue for sectioning.

Utilise a scoring system to analyse the staining and correspond this to the serum concentrations to identify a blood-borne treatment response biomarker. If murine toxicity is observed, the CAR T construct will be affinity matured to selectively target molecules expressed at a cancerous level. A tandem bi-specific CAR T cells may also be created to mitigate immune escape and enhance anti-tumour efficacy.

The search for an off-tumour cell target for CAR T therapy in glioblastoma has not yet been completed. The discovery and validation of the novel molecule as a biomarker of treatment response would be a unique finding.

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