Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

自体iPSC疫苗在体内诱导抗肿瘤反应

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作者:Nigel G Kooreman ,Youngkyun Kim ,Patricia E de Almeida ,Vittavat Termglinchan ,Sebastian Diecke ,Ning-Yi Shao ,Tzu-Tang Wei ,Hyoju Yi ,Devaveena Dey ,Raman Nelakanti ,Thomas P Brouwer ,David T Paik ,Idit Sagiv-Barfi ,Arnold Han ,Paul H A Quax ,Jaap F Hamming ,Ronald Levy ,Mark M Davis ,Joseph C Wu

Abstract

Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b+GR1hi myeloid cells. Adoptive transfer of T cells isolated from vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotes an antigen-specific anti-tumor T cell response. Our data suggest an easy, generalizable strategy for multiple types of cancer that could prove highly valuable in clinical immunotherapy.

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