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T cell phenotype changes associated with oncolytic virotherapy combined with Nivolumab

ABSTRACT: There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle invasive bladder cancer. We launched a Phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle invasive bladder cancer. The primary objective was to measure safety and the secondary objective to assess the antitumor efficacy of the combination. No dose limiting toxicity was encountered in 21 patients enrolled and treated. Combination treatment achieved a pathologic complete response rate of 42.1%, which was associated with baseline free E2F activity and tumor mutational burden, but not PD-L1 status. Although T cell infiltration was broadly induced following intravesical oncolytic virotherapy, the formation, enlargement and maturation of tertiary lymphoid structures (TLS) was specifically associated with complete response, supporting the importance of coordinated humoral and cellular immune responses. Together, these results highlight the potential of this combination regimen to enhance therapeutic efficacy in cisplatin-ineligible patients with muscle invasive bladder cancer, warranting its additional study as a neoadjuvant therapeutic option.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276366 | GEO | 2025/09/04

REPOSITORIES: GEO

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