- 作者: Tae Woo Kim; Chien-Fu Hung; Meizi Zheng; David A.K. Boyd; Liangmei He; Sara I. Pai; T.-C.Wu
- 作者服務機構: Departments of Pathology, Molecular Microbiology and Immunology, Oncology, Otolaryngology-Head and Neck Surgery, Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Md., USA
- 中文摘要: --
- 英文摘要: We have shown that DNA encoding the anti-apoptoticprotein Bcl-xL enhances E7-specific CD8+ T-cell re-sponses and DNA encoding pro-apoptotic protein cas-pase-3 suppresses E7-specific CD8+ T-cell responseswhen co-administered intradermally via gene gun withDNA encoding human papillomavirus type 16 (HPV-16)E7 linked to the sorting signal of the lysosome-associat-ed membrane protein type 1 (LAMP-1). E7 and LAMP-1are linked to form the chimeric Sig/E7/LAMP-1 (SEL).Because co-administration does not ensure delivery ofboth constructs to a single cell, we used pVITRO, a mam-malian expression vector with double promoters, to en-sure expression of both molecules in the same cell. Wevaccinated C57BL/6 mice with pVITRO-SEL-Bcl-xL,pVITRO-SEL-mtBcl-xL, pVITRO-SEL, or pVITRO-SEL-cas-pase-3 intradermally via gene gun and intramuscularlyvia injection. We demonstrated that vaccination withpVITRO achieved similar results to a co-administrationstrategy: that Bcl-xL enhanced the E7-specific CTL re-sponse and caspase-3 suppressed the E7-specific CTLresponse. In addition, we found intradermal vaccinationelicited significantly higher numbers of E7-specific CD8+T cells compared to intramuscular vaccination. Thus,intradermal vaccination with a pVITRO vector combiningan anti-apoptotic strategy (Bcl-xL) and an intracellulartargeting strategy (SEL) further enhances the E7-specificCD8+ T-cell response and guarantees co-expression ofboth encoded molecules in transfected cells.
- 中文關鍵字: --
- 英文關鍵字: --