Induced pluripotent stem cell-derived, genetically engineered myeloid cells as unlimited cell source for dendritic cell-related cancer immunotherapy

Abstract

Cancer immunotherapy is a unique treatment modality that uses the body's immune system to eliminate cancer cells. Immune checkpoint blockades, which inhibit immunosuppressive mechanisms to enhance cancer-reactive T-cell responses, have expanded cancer-treatment options because they can induce the regression of cancer that is refractory to existing treatments. However, many patients do not respond to immune checkpoint blockades, and new therapies are needed to overcome resistance to treatment. In recent years, researchers have begun developing methods to generate immune cells, which play an important role in eliminating cancer, from induced pluripotent stem cells (iPSCs) and have been administered to humans in clinical trials. This therapy can potentially replace existing cell-based cancer immunotherapies as the next generation of hybrid-cell therapies that combine immune cell therapy, regenerative medicine, and gene therapy. Previously, we constructed cytokine-dependent proliferating myeloid cells (induced pluripotent stem cell-derived proliferating myeloid cells; iPSC-pMCs) by inducing myeloid cell differentiation from iPSCs and subsequently introducing proliferation factors. Once constructed, the cells have proliferative potential, which eliminates the need for re-differentiating myeloid cells from iPSCs, resulting in an indefinite and stable supply of homogeneous cells with little investment of cost and effort. In this review, we discuss the potential of iPSC-pMC-based immune cell products as immune-stimulating agents for cancer that are refractory to checkpoint blockade.