One mechanism of NK cell anti-tumor activity is antibody-dependent cellular cytotoxicity (ADCC) induced via Fc receptor (CD16) binding to antibodies. Patients homozygous for a natural CD16 polymorphism, CD16-158V which displays higher IgG1 and IgG3 affinity, have improved clinical outcomes upon anti-tumor therapeutic antibody treatment.3-7
Only 10% of the human population is homozygous for this polymorphism8, suggesting that genetic manipulation of NK cells to express CD16-158V prior to adoptive transfer may improve clinical success not only of NK cell therapies but also anti-tumor IgG1 antibodies.
In vitro studies have demonstrated that NK cell lines engineered to overexpress CD16-158V have improved cytotoxicity against antibody-coated cancer cell lines9 supporting genetic reprogramming of NK cells; however, primary NK cells have historically been difficult to engineer.10
Non-viral engineering of NK cells using MaxCyte mRNA electroporation provides significant benefits including high efficiency and low toxicity as well as clinical scalability enabling rapid development of novel adoptive cell therapy approaches.11-13