Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Abstract

Encouraged by remarkable successes in preventing infectious diseases and by the well-established potential of the immune system for controlling tumor growth, active therapeutic immunization approaches hold great promise for treating malignant tumors. In recent years, engineered recombinant viral vectors have been carefully examined as genetic-immunization vehicles and have been demonstrated to induce potent T-cell-mediated immune responses that can control tumor growth. Very recent efforts suggest that lentivectors possess important advantages over other candidate recombinant viral vectors for genetic immunization. Here, we review the development of recombinant lentivectors and the characteristics of T-cell immune responses elicited by lentivector immunization, including the mechanism of T-cell priming with a focus on the role of skin dendritic cells and potential applications for tumor immunotherapy.

Fig. 1

Diagram of the recombinant lentivector. A represents the recombinant lentivector genome that will be packaged into viral particles. B are the packaging vectors expressing necessary components for assembling the recombinant lentivectors. RSV: Rous Sarcoma Virus; LTR: Long Terminal Repeat; RRV: Rev Responsive Element; TRIP: Triple-stranded DNA flap that contains a central polypurine tract sequence (cPPT) and the central termination sequence (CTS); CMVp, CMV promoter; WPRE:woodchuck hepatitis virus posttranscriptional regulatory element; VSV-G: Vesicular Stomatitis Virus Glycoprotein.

Fig. 2

Different DC subsets and mechanisms may be involved in priming CD8 T cell responses after immunization with engineered replication defective recombinant viral vectors and after wild type viral infections.