Gene delivery for leukemia treatment.

Abstract

Immunotherapy harnesses the cytotoxic capabilities of immune cells to recognize and eradicate cancerous cells, such as through expressing chimeric receptors that can bind to tumor antigens. However, successful gene delivery into primary immune cells for clinical use remains a challenge. Retroviral vectors and electroporation have been tested, but safety and cytotoxicity concerns limit their clinical applicability. Our goal is to identify non-viral nanoparticles as feasible vectors for delivering the anti-CD19-coding DNA into natural killer (NK) and cytokine-induced killer (CIK) cells. Expression of anti-CD19 receptor will direct them towards killing CD19-expressing acute lymphoblastic leukemia (ALL) cells. In this project, we evaluated the capabilities of nanoparticles P(MDS-co-CES), MK334A, F-peptide, PEI and LipofectamineTM, to transfect model suspension cell lines Jurkat and MOLT-4, and explored the effects of varying certain experimental parameters on transfection efficiency and cell viability. We found PEI and F-peptide to be most feasible and promising for the suspension cell lines. Future experiments will focus on improving their transfection efficiencies and reducing their cytotoxicities in human NK cell line and activated primary NK cells. Eventual success in developing a suitable nanoparticle vector will have significant implications for immunotherapy, since the chimeric receptor can be flexibly changed to target other tumor antigens.