Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs

作者：Susannah L. Hewitt, Ailin Bai, D. R. Shackleton Bailey, Kana Ichikawa, John Zielinski, Russell Karp, Ameya Apte, Kristen Arnold, Sima J. Zacharek, Maria S. Iliou, Khushbu Bhatt, Maija Garnaas, Faith Musenge, Ashley N. Davis, Nikhil Khatwani, Stephen Su, Graham MacLean, Samuel J. Farlow, Kristine Burke, Joshua P. Frederick · 发表于：Science Translational Medicine · 年份：2019 · DOI：10.1126/scitranslmed.aat9143 · 被引用次数：306 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、Cytokine Signaling Pathways and Interactions

T cells. IL-23/IL-36γ/OX40L triplet mRNA mixture triggered substantial immune cell recruitment into tumors, enabling effective tumor destruction irrespective of previous tumoral immune infiltrates. Last, combining triplet mRNA with checkpoint blockade led to efficacy in models otherwise resistant to systemic immune checkpoint inhibition. Human cell studies showed similar cytokine responses to the individual components of this mRNA mixture, suggesting translatability of immunomodulatory activity to human patients.