Publications by authors named "Lindsey J Coholan"
Article Synopsis
- Chimeric antigen receptor (CAR) T cells from universal donors can be rejected by the recipient's immune system, which impacts their effectiveness and longevity in treatment.
- The researchers created HLA class I-deficient T cells to avoid detection by mismatched CD8+ T cells and improved their NK cell tolerance using a specially designed molecule called dtHLA-E4.
- The optimized dtHLA-E4 molecule showed better surface expression, enhanced NK cell inhibition, and reduced recognition by CD8+ T cells while maintaining the ability to inhibit NK cells, making it a promising strategy for improving the persistence of CAR T cells in treatment.
Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells.
View Article and Find Full Text PDF