Exciting research by Nahi et al. showcases the safety and efficacy of infused autologous NK cells in patients with multiple myeloma after autologous stem cell transplantation. This opens new possibilities for using autologous NK cells in therapeutic settings, either alone or in combination with other treatments, providing hope for improved outcomes.
Moreover, CAR-NK cell therapies emerge as a promising alternative to CAR-T cell therapies, with the potential to overcome therapy-induced side effects. Globally, over 500 CAR-T and 17 CAR-NK cell trials are underway, investigating precise gene insertion or dual targeting methods with adapter CARs. CD19-specific CAR-T cells have shown promise against B-cell malignancies, while CAR-NK cells offer innate tumor-killing capacity alongside their CAR-dependent mechanism, potentially thwarting tumor immune escape. These cutting-edge approaches pave the way for more effective and targeted treatments for patients battling multiple myeloma.
Activated and expanded autologous NK cells were repeatedly infused in patients with multiple myeloma following autologous HSCT. Nahi et al studies’ reveals safety and efficacy metrics. It opens the door to using autologous NK cells in therapeutic settings, either alone or in conjunction with other treatments. The possibility of infusing several doses of ex vivo activated and expanded autologous NK cells in patients with multiple myeloma (MM) after autologous stem cell transplantation is discussed in this paper.
The use of CAR-NK cell therapies has emerged as a potential alternative to CAR-T cell therapies, due to their ability to overcome therapy-induced side effects. With over 500 CAR-T and 17 CAR-NK cell trials currently underway globally, CAR-immune cell therapies that use precise gene insertion or a dual targeting method with adapter CARs are being investigated. CD19-specific CAR-T cells have shown promise in treating B-cell malignancies, while CAR-NK cells offer an intrinsic tumor killing capacity in addition to their CAR-dependent killing mechanism, potentially impeding tumor immune escape mechanisms.
It was described in the findings from a first-in-human clinical trial in patients with multiple myeloma that used ex vivo activated and expanded NK cells after autologous HSCT (MM). Each patient received three escalating doses of activated and expanded NK cells at weekly intervals as part of the trial.
A feeder-free, GMP-compliant, automated, and closed system was used in this work to activate and expand NK cells from patients with malignant illnesses. 24 A first-in-human investigator-initiated clinical research in individuals who had autologous HSCT for MM was started based on this strategy. The clinical trial was set up as an open, single-arm experiment. The primary goal was to evaluate the NK cell-based product’s safety and tolerability. Secondary goals included determining disease response using monoclonal immunoglobulin levels, serum-free light chain, and MRD according to the consistent response criteria of the international myeloma working group (IMWG).
The NK cells developed a distinct activated phenotype after ex vivo activation and expansion, which included populations of CD56brightCD16+ Ki67+ HLA-DR+ NK cells. This unique profile was predicted to allow detection of the infused NK cells among peripheral blood NK cells immediately after infusion to the study individuals. The gradual development of the new NK cell population in a dose-dependent manner over 4 hours following infusion of the NK cell product was revealed by clustering analysis of data from these samples using t-distributed stochastic neighbor embedding (t-SNE). Furthermore, these cells exhibited high amounts of NKG2D, 2B4, TIM-3, and TIGIT, as well as remarkably low levels of CD38, similar to the NK cell infusion product. These findings point to phenotypic variation.
In conclusion, the findings described here open the door to more clinical trials with autologous NK cells, such as in situations when patients are not readily eligible for allogeneic NK cell-based therapies. In human cancer, this could include MRD and/or consolidation treatment. The current findings imply that autologous NK cells merit additional exploration in the context of future cancer treatment if adequately activated and expanded cells are used, whether or not in combination with other medications.
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