Dr. Bachanova on NK Cell Therapy in NHL

Veronika Bachanova, MD, PhD, professor, medicine, lead, Lymphoma Interdisciplinary Team, clinical director, cell therapies, section head, Malignant Hematology, University of Minnesota, discusses findings from a spatial analysis of the tumor microenvironment in patients with non-Hodgkin lymphoma (NHL) who received and responded to adoptive natural killer (NK) cell therapy.

A phase 1 study (NCT03019666) evaluated the efficacy of GDA-201, a novel nicotinamide allogeneic NK cell product, in 19 patients with relapsed/refractory NHL. The spatial analysis included lymphoma tumor site biopsies from evaluable patients who responded to the treatment.

Previously, this study demonstrated an overall response rate of 74% in the 19 total treated patients, with 13 patients achieving a complete response, Bachanova says. The findings from the tissue analysis, which were presented at the 2023 Transplantation and Cellular Therapy Meetings, showed that prior to treatment, the biopsies showed that NK cell infiltration of the lymph nodes occurred at low frequencies, Bachanova explains. After treatment with GDA-201, subsequent biopsies showed NK cell trafficking to the tumor microenvironment, with NK cells making up 10% to 15% of all tumor cells, Bachanova emphasizes.

However, rather than NK cells, the majority of cells detected in these biopsy infiltrates were T cells, both CD4 and CD8 subsets, including CD4+CD25+ regulatory T cells, Bachanova says. Although GDA-201 is a haploidentical NK cell product, these T cells were determined to be from the NK cell recipient, Bachanova notes.

This study also showed that T cells were detected early in the blood of the NK therapy recipients, Bachanova explains. Some subsets of the T cells had strong proliferation, as demonstrated by the high Ki67 expression observed in these biopsies, as well as the expression of trafficking receptors like CXCR3 and CCR4, which were upregulated on T cells after GDA-201 treatment, Bachanova says. These findings indicate that T cells from the blood may affect the trafficking of tumor-involved lymph nodes, Bachanova concludes.