Depleting Tumor Infiltrating Myeloid Cells to Enhance BsAb-driven T Cell Infiltration and Anti-tumor Immune Responses

초록

T cell-based immunotherapies including T-cell engaging bispecific antibodies (T-BsAb) and chimeric antigen receptor (CAR) T cells have proven clinical efficacy for human cancers. Though, the success has been limited to hematologic malignancies and a few solid tumors. To improve the efficacy of T-BsAb in solid tumors, we targeted tumor infiltrating myeloid cells (TIM) such as myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) and microvasculature within the tumor microenvironment (TME) in human xenograft models. Depletion of TIMs including granulocyte-derived MDSCs, monocyte-derived MDSCs, and TAMs and blocking VEGF signaling were associated with increase in tumor infiltrating T cells (TILs), accompanied by improved tumor control and mouse survival. In addition, we showed that corticosteroid exerted a profound effect on the TAMs, enhancing the anti-tumor response of T-BsAb while decreasing cytokine-release.