Allogeneic supercharged natural killer cells: an innovative approach for hematologic cancers

Chimeric antigen receptor-based immunotherapies, like CAR-T and CAR-NK cells, have shown success in treating blood cancers, but they come with challenges such as toxicity, antigen escape, and manufacturing complexity. In this study, we demonstrate that supercharged NK (sNK) cells represent a new, non-engineered immunotherapy platform with an enhanced ability to target and destroy both stem-like and mature tumor cells. sNK cells are created by co-culturing with osteoclasts and a probiotic formulation, sAJ2, resulting in strong activation and improved function. The study highlights that NK cells from multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have reduced numbers and impaired functionality compared to those from healthy donors. Attempts to reactivate NK cells from CLL patients using the sNK cell protocol failed, emphasizing the need for allogeneic sources. Through cytotoxicity assays, sNK cells showed superior effectiveness against a variety of blood cancer cell lines and patient-derived samples compared to IL-2-treated NK cells. Additionally, sNK cells produced significantly higher levels of pro-inflammatory cytokines and chemokines. These findings establish healthy donor-derived sNK cells as a promising off-the-shelf immunotherapy option, addressing the deficiencies seen in autologous NK cells in blood cancers.