Synergism between human apoptotic cell infusion and human chimeric antigen receptor (CAR)-T therapy in fighting solid human tumor in SCID Bg mice

Robust results from treatment of hematological malignancies with CAR-T were not replicated to date in solid tumors. We present a new mechanism of action which increases CAR-T efficacy in solid tumors. HeLa-CD19 was stably transduced with pLenti-PGK-V5-Luc-Neo and CAR was prepared using 3^rd generation CD19-CAR plasmids. SCID-Bg mice were injected intra-peritoneally with human HeLa-CD19-luciferase cells, apoptotic cells or vehicle, and CD19-CAR T cells or mock T cells. Mice survived 30±5 days, and mock treatment non significantly ameliorated their survival to 34±4 days. CAR T cell therapy significantly ameliorated their survival to 55±11 days. Single-cell analysis confirmed by flow cytometry revealed that macrophages that were associated with anti-tumor activity, completely disappeared during tumor progression, and reappeared during successful CAR T therapy. Apoptotic cells injected during tumor progression were able to stabilize the presence of macrophages as confirmed by single cell and flow cytometry analysis, and synergize with the anti-tumor CAR-T cell effect, resulting in significantly increased anti-tumor macrophage population and increased survival to 75±10 days (p<0.05).