Donor NKG2A/NKG2C Immunophenotype Influences the GMP-Compliant Manufacturing Potential of NK Cells for Adoptive Immunotherapy

Abstract

Simple Summary Natural killer cells are promising candidates for cellular therapy after allogeneic hematopoietic stem cell transplantation because they can help control malignant cells and viral infections with a low risk of graft-versus-host disease. However, the ability to manufacture these cells consistently under good manufacturing practice conditions may vary between donors, and donor-related factors are not well understood. In this proof-of-concept study, we investigated whether the baseline distribution of two natural killer cell receptors, NKG2A and NKG2C, was associated with successful cell manufacturing. We characterized 83 healthy donors and selected three donors with different receptor profiles for manufacturing using an automated closed system. Only the donor enriched in NKG2C-positive cells achieved the predefined manufacturing criteria. These findings suggest that donor immunophenotyping may be a promising factor to consider when evaluating donor suitability for natural killer cell manufacturing and warrants validation in larger studies.