A Phase II Study: Efficacy of the Gene Therapy of the MVA E2 Recombinant Virus in the Treatment of Precancerous Lesions (NIC I and NIC II) Associated with Infection of Oncogenic Human Papillomavirus

Cm, Corona Gutierrez; Tinoco, Alberto; M, López Contreras; Navarro, Tania; Calzado, Patricia; Vargas, Laura Rey; Reyes, L; Posternak, Roberto; Rosales, Ricardo

doi:10.1089/104303402753812520

Cited by 19 publications

(1 citation statement)

References 37 publications

(37 reference statements)

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“…While TA-HPV has previously been administered either intramuscularly (5), or intradermally (9, 10), the cervicovaginal route of administration has not been tested in humans. However, cervical administration of a recombinant E2 modified vaccinia Ankara (MVA) was well tolerated and was associated with lesion regression in a phase II trial with women with HPV disease (35). Taken together, the cervicovaginal route of administration of therapeutic HPV vaccinia virus vaccine such as TA-HPV may potentially be applicable to HPV associated lesions, particularly in advanced refractory cervical and head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

Sun

Peng

Liang

et al. 2016

Clinical Cancer Research

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Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination.

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Section: Discussionmentioning

confidence: 99%

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

Sun

Peng

Liang

et al. 2016

Clinical Cancer Research

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Prophylaktische und therapeutische Vakzinen gegen humane Papillomviren

Albers

Hoffmann²,

Klußmann

et al. 2010

HNO

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Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

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Medical treatment of cervical intraepithelial neoplasia II, III: an update review

Kietpeerakool

Srisomboon

2009

Int J Clin Oncol

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Cervical intraepithelial neoplasia (CIN) II, III is a preinvasive stage of squamous cell carcinoma of the uterine cervix. The standard treatment for CIN II, III consists of ablation and excision. However, nonsurgical treatment may be necessary for some women to preserve future reproductive potential. This review was conducted to summarize available published data on the efficacy and safety of medical treatment for CIN II, III. Based on existing studies, cyclooxygenase (COX)-2 inhibitors; indole-3-carbinol; and novel immunotherapy agents, including ZYC101a, MVA E2, and HspE7, have been observed as possessing therapeutic activity without any major treatment-related complications. These promising results provide important data for the future direction of clinical research.

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A Phase II Study: Efficacy of the Gene Therapy of the MVA E2 Recombinant Virus in the Treatment of Precancerous Lesions (NIC I and NIC II) Associated with Infection of Oncogenic Human Papillomavirus

Cited by 19 publications

References 37 publications

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

Prophylaktische und therapeutische Vakzinen gegen humane Papillomviren

Medical treatment of cervical intraepithelial neoplasia II, III: an update review

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