Cell reprogramming for immunotherapy

Abstract

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.