Intra Tumor Injection of CAR Engineered NK Cells Induces Tumor Regression and Protection Against Tumor Re Challenge
In this era of cancer immunotherapy, the long term goal of treatment is to eliminate tumor cells anywhere in the body through induction of a specific immune memory response. In addition to spontaneous cytotoxicity, ADCC, and cytokine release, NK cells contribute to an adoptive immune response through crosstalk with dendritic cells and T cells. To further characterize the NK cell induced adoptive response, aNK cells (formerly NK 92) were transduced with a retrovirus construct coding for a second generation anti murine CD19 CAR to create targeted activated NK 92 cells (mCD19.taNK) mCD19.taNK cells were injected intra tumorally (two injections of 5x106 cells, three days apart) into a murine model of syngeneic subcutaneous lymphoma, created by injecting 1x106 A20 cells into BALB/c mice. Tumor size was monitored over time, and mice showing complete tumor regression were re challenged with another subcutaneous contralateral injection of A20 cells. mCD19.taNK cells effectively killed murine cancer cells in vitro >60% killing at E:T ratio of 5:1) In vivo, intra tumor injection of mCD19.taNK induced significant tumor regression versus saline (tumor volumes of 342 mm3 and 936 mm3, respectively at day 16, p 80% mice remained free of tumor after 14 days. In conclusion, the human aNK cell line expressing an anti murine CD19 CAR (mCD19.taNK) can effectively kill CD19 positive murine cancer cells. Moreover, intra tumor injections of mCD19.taNK into a fully immunocompetent mouse model can induce tumor clearance and protection from tumor re challenge, suggesting induction of a memory "vaccine" effect after the injection of mCD19.taNK. Disclosures Boissel:NantKwest, Inc. Employment. Klingemann:NantKwest, Inc. Employment, Equity Ownership, Patents Royalties. Khan:NantKwest, Inc. Employment. Soon Shiong:NantKwest, Inc. Employment, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees.