Review

Gene Therapy (2007) 14, 847–862. doi:10.1038/sj.gt.3302947; published online 22 March 2007

Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

K Breckpot1,2, J L Aerts1,2 and K Thielemans1

1Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Brussels, Belgium

Correspondence: Dr K Breckpot or Dr J Aerts, Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Laarbeeklaan 103/E, Brussels 1090, Belgium. E-mails: karine.breckpot@vub.ac.be or joeri.aerts@vub.ac.be

2These authors contributed equally to this work.

Received 11 October 2006; Revised 1 February 2007; Accepted 2 February 2007; Published online 22 March 2007.

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Abstract

Lentiviral vectors have emerged as promising tools for both gene therapy and immunotherapy purposes. They exhibit several advantages over other viral systems in that they are less immunogenic and are capable of transducing a wide range of different cell types, including dendritic cells (DC). DC transduced ex vivo with a whole range of different (tumor) antigens were capable of inducing strong antigen-specific T-cell responses, both in vitro and in vivo. Recently, the administration of lentiviral vectors in vivo has gained substantial interest as an alternative method for antigen-specific immunization. This method offers a number of advantages over DC vaccines as the same lentivirus can in principle be used for all patients resulting in a significantly reduced cost and requirement for considerably less expertise for the generation and administration of lentiviral vaccines. By selectively targeting lentiviral vectors to, or restricting transgene expression in certain cell types, selectivity, safety and efficacy can be further improved. This review will focus on the use of direct administration of lentiviral vectors encoding tumor-associated antigens (TAA) for the induction of tumor-specific immune responses in vivo, with a special focus on problems related to the generation of large amounts of highly purified virus and specific targeting of antigen-presenting cells (APC).

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