BIOENGINEERING OF HUMAN PLURIPOTENT STEM CELLS FOR CHIMERIC ANTIGEN RECEPTOR IMMUNOTHERAPY

Immunotherapy as a treatment for cancers that do not respond to surgery, chemotherapy, or radiotherapy is a powerful technique in which immune cells are modified to exert cytotoxic effects against a specified tissue. A classic technique in immunotherapy is the use of chimeric antigen receptor (CAR) expressing immune cells (typically T lymphocytes; referred to as CAR-T) to drive an immune response against cancerous tissue. The efficacy of CAR-T is reduced in solid tumors due to limitations of T lymphocytes as an effector cell in a tumor microenvironment. In this study we demonstrate that CAR-neutrophils differentiated from genetically-modified human pluripotent stem cells displayed a strong cytotoxic effect against prostate-specific membrane antigen expressing LNCaP cells as a model for prostate cancer in vitro. Additionally, we found that modification of the neutrophil differentiation scheme resulted in suspended, CD4+ cells, demonstrating potential to rapidly generate T lymphocytes under a feeder-free, xeno-free scheme in vitro.