Abstract 939: A novel first-in-class common-gamma chain cytokine facilitates expansion of CD8+T cells and offers a superior cellular source for adoptive T-cell therapy

Isolation, ex vivo expansion followed by reinfusion of activated autologous lymphocytes is a successfully utilized and promising clinical treatment for both solid and liquid tumors. Although it has been routine for most clinical and experimental laboratories to rely on interleukin-2 (IL-2) to support T cell expansion this cytokine can result in substantial expansion and induction of regulatory T cells (Tregs), AICD, exhaustion and terminal differentiation. IL-2 signals when the three subunits of IL-2 receptor, namely α, β and γ form a heterotrimeric protein. We have recently described a novel re-targeted form of IL-2 which utilizes NKG2D rather than IL-2Rα to form the high affinity receptor complex for IL-2 signaling. This cytokine (OIL-2), targets signaling solely to NKG2D-expressing cells but its role in expanding CD8+ T cells for adoptive T cell therapy is unknown In direct comparison to IL2, OIL-2 resulted in significantly improved expansion of CD8+ T cells (70-fold in vs 345-fold increase in 3 weeks; p In conclusion we demonstrate that our first-in class cytokine is more effective and offers a superior method for ex vivo T cell expansion. OIL-2 mediated CD8+ T cell stimulation occur via an altered signaling complex which causes T cell metabolic re-programming. As a result, OIL-2 expanded T cells persist and offers better tumor clearance and provide superior protection against malignancy over T cells expanded through alternative protocols. Citation Format: Anirban Banerjee, Yizhan Guo, Sarah Hein, Alexander S. Krupnick. A novel first-in-class common-gamma chain cytokine facilitates expansion of CD8+T cells and offers a superior cellular source for adoptive T-cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 939.