Kurzfassung

While chimeric antigen receptor (CAR) or transgenic T-cell-receptor (TCR) redirected T cells have been elaborated for adoptive cellular therapy (ACT) in acute myeloid leukemia (AML), reprogramming of natural killer (NK) cells to AML is less advanced and currently limited to a CD33-CAR NK cell trial. Moreover, T-cell engineering is restricted to patient-derived T lymphocytes due to the risk of alloreactivity conferred by T cells from healthy donors, whereas allogeneic NK cells have been shown...While chimeric antigen receptor (CAR) or transgenic T-cell-receptor (TCR) redirected T cells have been elaborated for adoptive cellular therapy (ACT) in acute myeloid leukemia (AML), reprogramming of natural killer (NK) cells to AML is less advanced and currently limited to a CD33-CAR NK cell trial. Moreover, T-cell engineering is restricted to patient-derived T lymphocytes due to the risk of alloreactivity conferred by T cells from healthy donors, whereas allogeneic NK cells have been shown not to cause graft-versus-host reactivity and might thus allow the establishment of an ‘off-the-shelf’ product.
In the current study, we therefore explore a genetically engineered CD3+ variant of the established NK92 cell line. Following expression of different AML-reactive TCRs to redirect specificity cytotoxicity to AML cell lines and primary (patient-derived) AML blasts will be tested in vitro. Moreover, CD3+ NK 92 cells have been further engineered to stably express the CD8 coreceptor, and are being used to study CD8 dependent TCR-driven responses. In addition to AML CD3+ and CD3+CD8+ NK 92 cells will also be used to test TCR-mediated responses to other tumors such as e.g. melanoma.
 

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