BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
Chimeric antigen receptor expression in natural killer cell line NK-92 by transduction with lentiviral particles pseudotyped with the surface glycoproteins of the measles virus vaccine strain
Cancer immunotherapy with T-cells that carry chimeric antigen receptors is currently on cutting edge of modern oncology. Autotransplantation of T-lymphocytes with chimeric receptor specific for certain tumor antigen proves to be clinically effective, but costly. Linear carriers of chimeric antigen receptors based on natural killer NK-92 cell culture may be an affordable alternative, however, this culture is resistant to lentiviral transduction. Recently, lentiviral vectors, pseudotyped with surface glycoproteins of the measles virus vaccine strain, have recently been successfully applied for transduction of primary immune cells. The aim of the work was to assess the efficiency of transduction of NK-92 cells with lentivirus vectors, pseudotyped with measles F and H surface glycoproteins, as well as to establish optimal conditions for selection of NK-92 transduced with the chimeric receptor against CD20 and to evaluate the culture’s cytotoxic potential. The results showed that the maximum infectious titer is achieved using the H∆18 variant in combination with F∆30, and the use of the TBK1/IKKɛ inhibitor BX795 results in additional 3-fold increase in the infectious titer. CAR-expressing NK-92 were able to suppress the proliferation of CD20+ cell line Raji in lower effector-to-target ratios than unmodified NK-92.
Keywords: сellular immunotherapy, chimeric antigen receptors, CAR, lentiviral vectors, natural killer cells, linear cellular vessels, pseudotyping with measles glycoproteins