2025-10-28 イェール大学
<関連情報>
- https://www.yalecancercenter.org/news-article/yale-develops-dual-action-vaccine-to-combat-aggressive-merkel-cell-carcinoma/
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)01130-1
IL-7強化mRNAワクチンを用いて必須ウイルス腫瘍タンパク質を標的とすることで、メルケル細胞癌に対する持続的な免疫を誘導する Targeting an essential viral oncoprotein with an IL-7-enhanced mRNA vaccine induces durable immunity to Merkel cell carcinoma
Alexander Frey ∙ Kathryn Clulo ∙ Yuewei Fei ∙ … ∙ Harriet M. Kluger ∙ Kelly Olino ∙ Jeffrey J. Ishizuka
Cell Reports Published:October 1, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.116359
Graphical abstract
Highlights
- mRNA vaccines against an essential Merkel cell viral oncoprotein enhance immunity
- Vaccination is effective in mouse models and Merkel cell carcinoma patient samples
- Antigen loss limits efficacy in mouse models but not in MCC patients
- Co-encoded IL-7 mRNA boosts antigen-specific T cell memory and vaccine efficacy
Summary
Although mRNA technologies have reinvigorated cancer vaccine development, the identification of strong antigens with consistent tumor cell expression and generation of durable antigen-specific CD8+ T cell memory remain key challenges. We identified the Merkel cell carcinoma (MCC) large T antigen (LTA) as an optimal vaccine target, essential for tumor cell survival and immunogenic in a cancer with high unmet clinical need. We developed an mRNA vaccine to MCC-LTA in murine studies and patient samples. We showed that antigen loss develops rapidly and causes resistance in mouse models when immunogenic, but non-essential antigens are targeted. To improve T cell response 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 improved antigen-specific T cell expansion, memory differentiation, and tumor control. We propose that the principles of antigen essentiality and memory signal co-encoding may be adapted to improve the efficacy of mRNA therapeutics.
