Nonintegrating lentiviral vectors can effectively deliver ovalbumin antigen for induction of antitumor immunity.
It has been demonstrated that nonintegrating lentiviral vectors (NILVs) are efficient in maintaining transgene expression in vitro and in vivo. Gene delivery by NILVs can significantly reduce nonspecific vector integration, which has been shown to cause malignant transformation in patients receiving gene therapy for X-linked severe combined immunodeficiency. Strong and sustained immune responses were observed after a single immunization with NILVs carrying viral antigens. However, there is no report to date that evaluates the efficacy of NILVs in inducing antigen-specific antitumor immunity. Using a well-characterized tumor model, we tested in vivo immunization with a self-inactivating lentiviral vector harboring a defective integrase. A high frequency of ovalbumin peptide (OVAp1)-specific CD8(+) T cells and a substantial antibody response were detected in naive mice immunized with an NILV encoding an OVA transgene. Furthermore, this immunization method completely protected the mice against the growth of E.G7 tumor cells expressing the OVA antigen. Thus, this study provides evidence that immunization using NILVs can be a safe and promising approach for exploring cancer immunotherapy.
Hu
Biliang
B
Mork Family Department of Chemical Engineering and Material Science, University of Southern California, Los Angeles, CA 90089, USA.
Yang
Haiguang
H
Dai
Bingbing
B
Tai
April
A
Wang
Pin
P
D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D019427:HIV Integrase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D016233:Immunotherapy, Active; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010047:Ovalbumin / Q000235:genetics* / Q000276:immunology; D014161:Transduction, Genetic; D019076:Transgenes; D014759:Viral Envelope Proteins / Q000235:genetics; D016662:Virus Integration
D000941:Antigens; D019496:Cancer Vaccines; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D010047:Ovalbumin; D019427:HIV Integrase