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Targeting an essential viral oncoprotein with an IL-7-enhanced mRNA vaccine induces durable immunity to Merkel cell carcinoma

ABSTRACT: mRNA technologies have reinvigorated cancer vaccine development, but the optimal antigenic targets remain unclear. Further, generation of memory CD8+ T cell responses, critical for durable immunity, remains a challenge. We identified the Merkel cell carcinoma (MCC) Large T Antigen (LTA) as an exemplar target antigen, required for tumor cell survival and immunogenic in a cancer with rising incidence and high unmet need. We developed an mRNA vaccine to MCC-LTA in murine studies and MCC patient samples and showed that antigen loss developed rapidly and caused resistance when the antigen was not essential for tumor survival. To improve T cell response quality and durability, we co-encoded LTA and IL-7, co-localizing proliferative and memory signals spatially and temporally with antigen exposure. IL-7-containing mRNA vaccines enhanced T cell expansion, memory differentiation and sustained tumor control. We propose that antigen essentiality and signal co-encoding may be adapted to improve the efficacy of mRNA therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305197 | GEO | 2025/08/13

REPOSITORIES: GEO

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