Immunotherapy is a rapidly evolving field within oncology. Current immunotherapies, such as immune checkpoint inhibitors (CPI), primarily target the interaction of cancer cells with the adaptive immune system, permitting T-cells to surveil and attack malignant cells. While these approaches have provided major therapeutic benefits for patients, there is still a large unmet need as some tumors are not responsive to CPI and a subpopulation of patients become refractory to checkpoint therapy.  To address this, a next generation of immunotherapies targeting the innate immune system, and specifically the activation of phagocytes is entering clinical evaluation.

Macrophages, one of the most abundant tumor-infiltrating immune cells, are professional antigen presenting cells that specialize in the phagocytosis of apoptotic cells, cellular debris, and foreign antigens. Phagocytosis by macrophages is regulated by anti-phagocytic "Don't Eat Me" (DEM) and pro-phagocytic "Eat Me" (EM) signals, expressed on healthy and apoptotic or senescent cells respectively. Cancer cells evade macrophage-mediated clearance by exploiting expression of DEM signals on their cell surface.  Therefore, blocking DEM or stimulating EM signals to activate tumor-associated macrophages (TAMs) is an exciting novel approach for cancer treatment.

Previous studies have demonstrated that a genome-wide CRISPR screen of cancer cells co-cultured with murine macrophages could identify novel DEM and EM signals beyond the well-known CD47-SIRPa ligand receptor pair. At DEM BioPharma, we have further evolved and humanized this target discovery platform by co-culturing human myeloid phagocytes with cancer cells (CHoMP platform) to identify novel and potentially targetable DEM and EM signals. Here, we discuss the merits of the co-culture CRISPR screening approach and initial results from an early CHoMP CRISPR platform screen.