A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

Peng, Shiwen; Tomson, Todd T.; Trimble, Cornelia L.; He, Liangmei; Hung, Chien-Fu; Wu, T. C.

doi:10.1038/sj.gt.3302646

Cited by 43 publications

(48 citation statements)

References 25 publications

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“…For instance, since E6 and E7 are both important for the malignant transformation of HPV-associated neoplasia and are coexpressed in nearly all HPV-associated tumors, both antigens represent ideal candidates for codon optimization. We have previously demonstrated that coadministration of CRT/E6 and CRT/E7 vaccines generates a better anti-tumor effect compared to the administration of either CRT/E6 DNA or CRT/E7 DNA [25]. In view of this observation, it is likely that a combination of DNA vaccines encoding codon-optimized E6 and codon-optimized E7 may provide more potent antitumor effects than vaccination with codon-optimized E6 alone.…”

Section: Discussionmentioning

confidence: 95%

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Lin

Tsai

et al. 2006

J Biomed Sci

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SummaryThe HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8 + T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

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Section: Discussionmentioning

confidence: 95%

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Lin

Tsai

et al. 2006

J Biomed Sci

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“…We have demonstrated that mice vaccinated with CRT/E6 DNA generated significant E6-specific CD8 + T-cell immune responses and could protect vaccinated mice from challenge with E6-expressing TC-1 tumors compared to vaccination with wild-type E6 DNA. 6,7 Thus, DNA vaccines encoding CRT are capable of significantly enhancing the DNA vaccine potency.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice

et al. 2008

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“…In a preclinical study with SFV replicon particles we also demonstrated higher anti-tumor immunity with the inclusion of both E6 and E7 compared to either oncogene alone. 43 Furthermore, in patients with HPV neoplasia both E6 and E7-specific CD8 + T cell responses have been correlated with better prognostic value. 44 Despite the lower immunogenicity observed with the variant of E7, administration of either a 0.2 or 0.05 ug dose of E7sh resulted in a significant delay in tumor growth compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Wall

Ljungberg

et al. 2018

OncoImmunology

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Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7. Our group pioneered a recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit of this alphavirus vector-based vaccine platform is its high potency. DNA vaccines on the other hand, have a major advantage with respect to ease of production. In this study, the benefits associated with both SFV-based vaccines and DNA vaccines were combined with the development of a DNA-launched RNA replicon (DREP) vaccine targeting cervical cancer. Using intradermal delivery followed by electroporation, we demonstrated that DREP encoding for E6,7 (DREP-E6,7) induced effective, therapeutic antitumor immunity. While immunizations with a conventional DNA vaccine did not prevent tumor outgrowth, immunization with a 200-fold lower equimolar dose of DREP (0.05 µg of DREP) resulted in approximately 85% of tumor-free mice. To overcome the safety concern of potential malignant transformation at the vaccination site, we evaluated the anti-tumor effect of a DREP vaccine encoding a shuffled version of E7 (DREP-E7sh). DREP-E7sh delayed tumor growth yet not to the same extent as DREP-E6,7. In addition, inclusion of a helper cassette and an ER targeting signal (sigHelp) did not significantly further enhance the suppression of tumor outgrowth in the long term, albeit exhibiting better tumor control early after immunization. Collectively, this study points towards the clinical evaluation of DREP encoding HPV antigens as a potent immunotherapy for patients with HPV16 (pre)-malignancies.

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A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

Cited by 43 publications

References 25 publications

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

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