NKT cells are immune cells that are capable of directly attacking cancer cells and activating other immune cells via an adjuvant process. Activated NKT cells produce various types of cytokines that elicit activation of natural killer (NK) cells and maturation of dendritic cells of the innate immune system. Mature dendritic cells then cause killer T cells of the adaptive immune system to proliferate and become activated, resulting in a synergistically enhanced anti-tumor effect. By activating innate immune system, NKT cells are capable of killing major histocompatibility complex (MHC)-negative cancer cells, which T cells are incapable of killing. This is one feature that is unique to iPS-NKT cell therapy.
Despite their significant anti-cancer potential, current cell therapies using NKT cells have their downsides. Unlike with chimeric antigen receptor T-cell therapy (CAR-T, where patients’ own T cells are employed to treat cancer), they are extremely difficult to harvest from the body and culture and grow to quantities that are adequate for clinical treatment, since NKT cells make up only from 0.01% to 0.1% of total blood T cells. Overcoming this limitation is what prompted RIKEN to initiate research in iPS cell technology. Dr. Haruhiko Koseki, Group Director of the Laboratory for Developmental Genetics, and associates sought to realize the timely production of NKT cells in sufficient and stable quality and quantity for treatment with iPS cell technology, in which unlimited numbers of NKT cell derived pluripotent stem cells are grown and then induced to re-differentiate into NKT cells.
This is a RIKEN-led project from the “Center for development of cancer immunotherapy technology by regenerating natural killer T-cells,” which was accepted as a Center for Clinical Application Research on Specific Disease/Organ (Type B) of the Research Center Network for Realization of Regenerative Medicine of the Japan Agency for Medical Research and Development. This project is also part of the RIKEN Program for Drug Discovery and Medical Technology Platforms. An investigator-initiated clinical trial targeting head and neck cancers was started in June 2020.