Abstract
Chimeric antigen receptor (CAR) T cell therapy is a novel cancer treatment currently being successfully used against blood-based malignancies, however, efficacy in solid tumours has not yet been achieved. A potential solution to this is by co-delivery of Natural Killer (NK) cells, components of the immune system that have an innate role in targeting malignant cells. NK cells are a promising candidate for therapeutics due to these innate anti-cancer characteristics and the potential to be delivered as an “off-the-shelf” option, contrasting the bespoke nature of CAR T cells. However, their potential negative effects on CAR T cells needs further investigation, as their natural lytic activity may also cause CAR T cell lysis.
The aim of this project was to determine whether NK cells lyse CAR T cells when expanded in an in vitro environment, simulating a therapeutic expansion setting. Total T cells (CAR-transduced and un-transduced) were co-cultured with NK cells for 4, 8, 24 and 48 hours. This was performed at different NK cell to T cell ratios (3:1, 1:1, 0.3:1, 0.25:1, 0.1:1) for each timepoint using cells derived from two donors and in triplicate repeats. Total T cells cultured under the same conditions without NK cells were used as controls. Lysis was measured using viability dye and flow cytometry.
Statistical significance was determined using two-way ANOVAs, with no significant differences in growth and population ratio changes between controls and co-cultures for both transduced and un-transduced T cells (P-values ranging from 0.404 – 0.203), apart from the 1:1 co-culture for one of the donors (P-value of 0.008). This provides foundational evidence for the further investigation into whether these two therapeutic cell types could be delivered to a patient simultaneously, as opposed to a staggered approach. Future experiments would involve monitoring potential antagonistic interactions between the cell types in mouse models.