Abstract 4144: Improvement of tumor cell transduction with lentiviral vectors using chemical and cell targeting approaches

Although lentiviral transduction methods are widely used in cancer research their application is frequently hindered by the low transduction efficiency seen for a number of different cell types, in particular primary cells. We have previously reported that a mixture of poloxamer synperonic F108 and polybrene combines reduced toxicity and increased lentiviral gene delivery into a range of different primary cell cultures (1). We now report further improvement in efficiency through a novel combination of the poloxamer-based adjuvant with a modified lentiviral envelope. The envelope was rendered cell specific by fusing monoclonal antibody fragments directed against specific cell-surface epitopes with the viral attachment glycoprotein VSV-G. For specific cellular targeting we inserted chimeric antiCD30 or antiEGFR antibody-VSV-G fusion proteins into the lentiviral genome. The combination of VSV-G-fused antibody fragments against specific tumor cell antigens and the improved adjuvant resulted in a 3-fold higher transduction rate using a GFP reporter containing lentivirus in CD30-positive lymphoma and EGFR-positive epithelial breast cancer cells. The combination of optimized transduction enhancer molecules and retargeted lentiviral vectors enabled quantitative transduction of previously hard-to-transduce cell types. When mixtures of antigen-negative and antigen-positive tumor cells were selected the modified lentivirus particles showed a preference for infecting antigen-positive cells by a factor 4. These results demonstrate that improvements in both chemical charge protecting adjuvants and membrane targeting can lead to increased transduction efficiency without a loss of specificity. The combination of chemical adjuvant and envelope design can lead to the optimization of lentiviral transductions in large-scale systems. *1. Höfig I, Atkinson MJ, Mall S, Krackhardt AM, Thirion C, Anastasov N. Poloxamer synperonic F108 improves cellular transduction with lentiviral vectors. J Gene Med. 2012 Aug;14(8):549-60. Citation Format: Ines Höfig, Michael J. Atkinson, Christian Thirion, Natasa Anastasov. Improvement of tumor cell transduction with lentiviral vectors using chemical and cell targeting approaches. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4144. doi:10.1158/1538-7445.AM2013-4144