Chimeric antigen receptor T (CAR T) cell therapy’s profound clinical success in B-cell lymphoma and multiple myeloma cancer patients has not translated to solid tumors, which comprise 90% of cancer cases worldwide. A key barrier for CAR T therapy in solid tumors is their immunologically cold microenvironment which blocks T cells from functioning as cancer cell killers. Engineered myeloid cells are being explored to overcome these limitations as monocytes and macrophages efficiently traffic deep into solid tumors. Autologous macrophages for clinical use are limited by the maximum number of cells that can be obtained from leukapheresis and the difficulty of genetically engineering these cells using established techniques. Here we present induced pluripotent stem cell (iPSC)-derived macrophages as a platform to overcome these limitations. We generated an iPSC line with bi-allelic knockout of the beta-2-microglobulin (B2M) gene. B2M-knockout (B2M-/-) iPSCs efficiently differentiate into macrophages that do not express MHC-I molecules while maintaining expression of MHC-II, preserving their ability to present antigens to T and B cells. When co-cultured with PBMC-derived T cells, wildtype iPSC-derived macrophages, but not B2M-/- iPSC-derived macrophages, upregulate T cell early activation marker CD69 (2.52- and 0.88-fold, respectively), suggesting that the B2M-/- iPSC-derived macrophages do not cause T cell-mediated alloreactivity. B2M-/- iPSC-derived macrophages transfected with mRNA encoding the immunostimulatory cytokine IL-12 and co-cultured with PBMC-T cells showed greater cell lysis of MDA-MB-231 breast adenocarcinoma cells (12% vs 2%; p=0.01) andSK-OV-3 ovarian adenocarcinoma cells (62% vs. 33%; p=0.03) compared to mock transfected macrophages. When co-cultured with IL-12 mRNA transfected B2M-/- iPSC-derived macrophages, ROR1-CAR T cells showed greater cell lysis of MDA-MB-231 cells (46%) compared to the ROR1-CAR T cells alone (29%, p=0.001). These results suggest that engineered iPSC-derived macrophages may prove useful to translate CAR T therapy to treat solid tumors by delivering potent immunomodulatory proteins such as IL-12 to the solid tumor microenvironment while avoiding host-versus-graft alloreactivity.