Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe.
DNA vaccines have emerged as an attractive approach for antigen-specific cancer immunotherapy. We have previously linked Mycobacterium tuberculosis heat shock protein 70 (HSP70) to human papillomavirus type 16 (HPV-16) E7 in the context of a DNA vaccine. Vaccination with DNA encoding E7/HSP70 has generated a dramatic increase of E7-specific CD8+ T cell precursors and a strong antitumor effect against E7-expressing tumor (TC-1) in vaccinated mice. The success of our strategy has led to two phases I/II clinical trial proposals in patients with HPV-16 associated high-grade squamous intraepithelial lesion (HSIL) of the cervix and in patients with advanced HPV-associated head and neck squamous cell carcinoma (HNSCC). To translate our HPV DNA vaccines into the clinical domain, the efficacy of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and of various routes of administrations were assessed in mice. Our results indicated that pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered via gene gun generated the highest number of E7-specific CD8+ T cells. In addition, DNA vaccination via gene gun required the least dose to generate similar or slightly better antitumor effects compared to needle intramuscular (i.m.) and biojector administrations. Thus, our data suggest that DNA vaccination via gene gun represents the most potent regimen for DNA administration.
Trimble
Cornelia
C
Department of Obstetrics and Gynecology, The Johns Hopkins Medical Institution, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lin
Cheng-Tao
CT
Hung
Chien-Fu
CF
Pai
Sara
S
Juang
Jeremy
J
He
Liangmei
L
Gillison
Maura
M
Pardoll
Drew
D
Wu
Lee
L
Wu
T-C
TC
D000818:Animals; D000918:Antibody Specificity; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010212:Papilloma / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D027383:Papillomaviridae / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D019496:Cancer Vaccines; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma