Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

• DOI: 10.1126/sciadv.abm1032
• Publication Date: 2022-03-02T18:59:07Z
• Authors: Amanda M. Nash; Maria I. Jarvis; Samira Aghlara-Fo...; Sudip Mukherjee; Andrea Hernandez; Andrew D. Hecht; Peter D. Rios; Sofia Ghani; Ira Joshi; Douglas Isa; Yufei Cui; Shirin Nouraein; Jared Z. Lee; Chunyu Xu; David Y. Zhang; Rahul A. Sheth; Weiyi Peng; Jose Oberholzer; Oleg A. Igoshin; Amir A. Jazaeri; Omid Veiseh
• Keywords: Systemic administration; Proinflammatory cytokine; Cytokine Release Syndrome

Proinflammatory cytokines have been approved by the Food and Drug Administration for treatment of metastatic melanoma renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects limit long-term benefits. To overcome these limitations, we developed a clinically translatable delivery platform composed polymer-encapsulated human ARPE-19 (RPE) cells produce natural cytokines. Tumor-adjacent administration capsules demonstrated predictable dose modulation with spatial temporal control enabled peritoneal cancer immunotherapy without toxicities. Interleukin-2 (IL2)–producing factory eradicated tumors ovarian colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this elicited T cell responses NHPs, consistent reported biomarkers efficacy toxicity. Combined, our findings demonstrate safety IL2 factories preclinical animal models provide rationale future testing