Vaccination targeting the novel endogenous tumor-associated antigen Gpr149 induces protective immunity against checkpoint inhibitor-refractory SB28 glioblastoma

ChAdOx1/MVA vaccination targeting the endogenous glioblastoma antigen Gpr149 in SB28 mice generated dominant CD8+ T cell responses and achieved long-term survival in 50% after intracranial challenge.

• Why it matters: Glioblastoma poorly induces CD8+ T cells, and preclinical vaccine work is limited by models lacking immunologically stringent, endogenously expressed antigen targets.
• What they did: Using RNA sequencing and whole-exome sequencing, the study identified five candidate TAAs in SB28 (including Gpr149) and validated expression by RT-qPCR, then tested ChAdOx1/MVA vaccines encoding each antigen with epitope mapping and cytotoxicity assays.
• The result: Gpr149-targeted vaccination, unlike vaccines for the other TAAs, significantly prolonged median survival and produced CD8+ T cells that lysed wild-type SB28 but not Gpr149-knockout cells via the Gpr149128-135 epitope VCYNFYTM.

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