Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells
Recent advances in cancer immunotherapy emphasize the need for an efficient method to genetically modify effector lymphocytes to express exogenous “synthetic” genes. NK cells represent 10–20% of total lymphocytes in the peripheral blood of humans and play an essential role in clearing infections and malignant cells. A significant number of NK cells express and utilize non-clonotypic receptors that recognize cognate ligands expressed on a broad spectrum of target cells. Thus, NK cells can be utilized as potent immunotherapeutic tools with fewer limitations. Considerable amount of progress in improving effector functions through genetic manipulations has been centered around T cells. However, a similar technological and translational exploration on NK cells is lacking. One major constrain is the significantly low efficiency of lentiviral-mediated gene transductions into primary human or mouse NK cells. We found that dextran, a branched glucan polysaccharide, significantly improves the transduction efficiency of human and mouse primary NK cells. This highly reproducible methodology offers an approach that can help to improve gene delivery into NK cells and thereby cancer immunotherapy.
KeywordsTransduction Primary NK cells Dextran Lentivirus Genetically modified Immunotherapy
Funding Support: We thank Lucia Sammarco and her Lulu’s Lemonade Stand for inspiration, motivation, and support. This work was supported in part by Ann’s Hope Melanoma Foundation (S.M. and M.S.T.); NIH R01 AI102893 (S.M.) and NCI R01 CA179363 (S.M. and M.S.T.); HRHM Program of MACC Fund/Children’s Hospital of Wisconsin (S.M.), Nicholas Family Foundation (S.M.); Gardetto Family (S.M.); MCW-Cancer Center-Large Seed Grant (S.M. & M.S.T.); and MACC Fund/Children’s Hospital of Wisconsin (M.S.T. and S.M.).
- 7.Liu E, Tong Y, Dotti G, Shaim H, Savoldo B, Mukherjee M, Orange J, Wan X, Lu X, Reynolds A, Gagea M, Banerjee P, Cai R, Bdaiwi MH, Basar R, Muftuoglu M, Li L, Marin D, Wierda W, Keating M, Champlin R, Shpall E, Rezvani K (2018) Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia 32(2):520–531. https://doi.org/10.1038/leu.2017.226CrossRefPubMedGoogle Scholar
- 9.Zhang C, Oberoi P, Oelsner S, Waldmann A, Lindner A, Tonn T, Wels WS (2017) Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol 8:533. https://doi.org/10.3389/fimmu.2017.00533CrossRefPubMedPubMedCentralGoogle Scholar