Abstract 2581: IL-15 expressing MSCs for NK cell-mediatedcancer immunotherapy

Abstract

Abstract Mesenchymal stem cells (MSCs) offer the possibility of achieving highly selective, tumor-targeted drug delivery because of their ability to home to malignant tissues. IL-15 is currently in clinical trial either alone or as an adjuvant for certain types of metastatic solid tumors. Systemic administration of IL-15 is associated with severe toxicities including hemodynamic imbalance, lymphopenia, and other cytokine-related complications. We hypothesized that tumor targeted delivery of IL-15 using MSCs can improve efficacy and reduce toxicity associated with IL-15. MSCs were engineered to express IL-15 using a lentiviral system (pLenti-C-Myc-DDK-P2A-Puro vector; Invitrogen) tagged with C-terminal MYC/DDK tag for easy detection and purification with anti-DDK antibody. We achieved stable transfection of IL-15 in MSCs (5.7 ng/106 MSCs in 24 hrs; ELISA). Bioactivity of secreted IL-15 was confirmed by splenocyte proliferation assay. We then tested the anticancer activity of IL-15 secreting MSCs in a syngeneic LL/2 lung cancer model. Animals treated with IL-15 secreting MSCs demonstrated significant inhibition of tumor growth and prolonged survival compared to mice treated with IL-15 alone. It was further demonstrated that IL-15 expressing MSCs enhance tumor infiltration of various immune cells. These studies demonstrate the potential of developing novel MSC-based immunotherapy constructs with reduced toxicity. Citation Format: Drishti Sehgal, No'ad Shanas, Swayam Prabha. IL-15 expressing MSCs for NK cell-mediatedcancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2581.