Harnessing TRACK-NK Cells for Non-Small Cell Lung Cancer Immunotherapy: A Focused Review

The abstract discusses a study on non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths globally. The research explores the potential of utilizing an immune response to extend the lives of NSCLC patients using checkpoint inhibitors. A specific type of natural killer (NK) cells, known as TRACK-NK cells, which are reactive to tumors and upregulate PD-L1, were identified. These cells are more effective in combating tumor cells than their PD-L1 negative counterparts. The use of an anti-PD-L1 antibody, atezolizumab, was found to enhance the activity of TRACK-NK cells, leading to increased degranulation and IFN-gamma secretion.

The study also examined the efficacy and safety of using allogeneic TRACK-NK cells that were engineered to express a soluble form of IL-15 (sIL-15) to treat NSCLC, with or without atezolizumab. These cells were derived from umbilical cord blood, expanded substantially, and engineered to express sIL-15 and PD-L1. The final product showed increased expression of PD-L1, CD25, and CD69 compared to non-transduced cells or those transduced without cytokine activation.

Post cryopreservation, the TRACK-NK cells maintained high recovery and viability. In vitro assays demonstrated that TRACK-NK cells were significantly more potent in cytotoxicity against a human NSCLC cell line than non-transduced NK cells and those transduced with sIL-15 alone.

In vivo studies using immunodeficient mice with human A549 metastatic NSCLC showed that the infusion of TRACK-NK cells led to a substantial suppression of tumor growth. Dose response studies indicated that a higher dose of TRACK-NK cells was more effective in controlling tumor growth, and the combination of TRACK-NK cells with atezolizumab provided superior tumor control.

Safety assessments in mice without tumors showed no significant adverse effects on body weight, temperature, liver enzymes, kidney function, or blood counts, and no cytokine release syndrome was observed.

In conclusion, the research indicates that the use of allogeneic TRACK-NK cells is safe and non-toxic, with enhanced in vitro cytotoxicity against NSCLC and improved in vivo tumor control, particularly when combined with atezolizumab. Given the natural tendency of activated NK cells to migrate to the lungs, the TRACK-NK platform is poised for clinical trials to treat patients with relapsed and refractory NSCLC.