Abstract:
: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.
journal_name
Vaccinejournal_title
Vaccineauthors
Trimble C,Lin CT,Hung CF,Pai S,Juang J,He L,Gillison M,Pardoll D,Wu L,Wu TCdoi
10.1016/s0264-410x(03)00275-5subject
Has Abstractpub_date
2003-09-08 00:00:00pages
4036-42issue
25-26eissn
0264-410Xissn
1873-2518pii
S0264410X03002755journal_volume
21pub_type
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