Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

• Published in: Seminars in immunopathology 2019-01, Vol.41 (1), p.59-68
• Main Authors: Saetersmoen, Michelle L., Hammer, Quirin, Valamehr, Bahram, Kaufman, Dan S., Malmberg, Karl-Johan
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Autografts; Biomedical and Life Sciences; Biomedicine; Biopharmaceuticals; Cancer; Cell Movement - immunology; Cell- and Tissue-Based Therapy - methods; Cellular Reprogramming - genetics; Cellular Reprogramming - immunology; Chimeric antigen receptors; Cytotoxicity; Cytotoxicity, Immunologic; DNA methylation; Fibroblasts; Gene expression; Genetic Engineering; Genome editing; Graft versus host disease; Humans; Immune system; Immunology; Immunotherapy; Immunotherapy, Adoptive - methods; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Internal Medicine; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Natural killer cells; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - therapy; Pluripotency; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Receptors, Chimeric Antigen - genetics; Receptors, Chimeric Antigen - metabolism; Review; Stem cells; Stored products; T-Cell Antigen Receptor Specificity - immunology; Tumors
• ISSN: 1863-2297; 1863-2300
• DOI: 10.1007/s00281-018-0721-x

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic “universal” cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.