NantKwest is launching the first-in-human Phase 1 clinical trial assessing the effects of its investigational CD19 t-haNK cell therapy in people with locally advanced B-cell lymphoma. The trial follows the U.S. Food and Drug Administration‘s approval of NantKwest’s investigational new drug (IND) application for the therapy.
Natural killer (NK) cells are key players in the fight against tumors. But their insufficient numbers and short lifespan have limited their applicability as a treatment against cancer.
CD19-t-haNK cell therapy is an immunotherapy designed to enhance the killing activity of natural killer cells against tumor cells. It is an off-the-shelf treatment, meaning that the therapy can be used in all people without the need for individualized patient matching.
The approach involves collecting a donor’s NK cells and genetically modifying them to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein. In this case, the cells are engineered to target the CD19 protein, a cell surface marker that is present in healthy and malignant B-cells.
Additionally, the cells carry the CD16 protein, important for activating the body’s innate immune system, and the subsequent killing of tumor cells. The CD16 protein binds to a previously administered anti-cancer antibody, enhancing its response against the tumor.
Researchers note that innate immunity refers to a person’s general immune response against pathogens, while adaptive immunity refers to a specific immune response against a pathogen that involves memory.
Previous preclinical studies used cell lines and mouse models for B-cell lymphomas with different levels of CD19. The results confirmed the killing activity of CD19 t-haNK cells, and showed it can be successfully used in combination with other targeted approaches.
“Based on extensive and encouraging preclinical results, we have enhanced our ability to modularly combine this proprietary off-the-shelf t-haNK-based therapy with a wide range of monoclonal antibodies using this multi-targeted approach,” Patrick Soon-Shiong, chairman and CEO of NantKwest, said in a press release.
“We are now ready to transition this innovation in NK cell based therapeutics to a Phase I human clinical trials designed to assess the safety, tolerability and efficacy of CD19 t-haNK cell therapy in advanced B-cell lymphoma,” he said.
After completing the safety phase, NantKwest “intends to combine this CD19 t-haNK cell therapy with other synergistic, immunomodulatory agents as part of an integrative, combination therapy approach that we describe as the NANT Cancer Vaccine to further enhance the synergistic effectiveness of this novel therapeutic intervention,” Soon-Shiong added.