Perspectives for therapeutic HPV vaccine development

Yang, Andrew; Farmer, Emily; Wu, T. C.; Hung, Chien Fu

doi:10.1186/s12929-016-0293-9

Cited by 171 publications

(171 citation statements)

References 101 publications

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“…Montanide adjuvants have been used for formulation of different protein antigens including long peptides of HPV16 E6 and E7 [26,27]. The formulations of HPV 16 E6 and E7 peptides with Montanide adjuvants have been used as HPV therapeutic vaccines in clinical trials [28,29]. There are limited studies regarding the effect of Montanide ISA 266.…”

Section: Discussionmentioning

confidence: 99%

Preparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate

Shirazi

Roohvand

Arashkia

2016

vacres

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Introduction: Human papillomavirus (HPV) 16 E7 protein is expressed constitutively by HPV-infected tumor cells. Mutant versions of E7 are considered as safer candidates for immunotherapy of cervical cancer. Different strategies including formulation with adjuvants are used to induce a potent immune response against antigenic proteins. Methods: In this experimental study, we used Escherichia coli as a host to recombinantly express wild-type E7 and its mutant non-oncogenic form as E7GGG. We formulated both antigens with Montanide ISA 266 adjuvant and evaluated IFN-γ and IL-4 cytokines and antibody levels and also tumor regression in tumor-harboring C57BL/6 mice. Results: It was demonstrated that formulation of E7 and E7GGG antigens with Montanide ISA 266 resulted in a Th2-biased immune response. In the therapeutic mouse model, these formulations resulted in significant tumor regression compared to the control group. Conclusion: The formulation of the wild-type E7 and mutant E7GGG with Montanide ISA 266 might not be an optimal approach to regress TC-1 induced tumor; however, such combinations might be considered as an additive approach for stimulating the immune responses.

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Section: Discussionmentioning

confidence: 99%

Preparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate

Shirazi

Roohvand

Arashkia

2016

vacres

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“…Other biomarkers may be used after HPV testing in the future to improve the specificity of screening, which may reduce the number of women being unnecessarily referred to secondary care for colposcopy [18].…”

Section: Cervical Cancer Prevention In Low Resource Settingsmentioning

confidence: 99%

Prevention of Cervical Cancer

Achampong¹,

Kokka²,

Doufekas³

et al. 2018

JCT

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Cervical cancer is the fourth most common cancer in women and is responsible for 275,000 deaths worldwide each year. The burden of this disease lies in the developing world. However it is arguably the most preventable cancer. The Human Papilloma Virus (HPV) is responsible for almost all cases of Cervical Cancer. HPV is sexually transmitted and has a lifetime cumulative risk of infection of 80%. National Cervical cytology screening programmes are used to detect cervical abnormalities, lesions and early cancers in as many eligible women as possible, saving lives and reducing morbidity. However uptake of screening is declining, and screening programmes have not been implemented in lower resource countries due to the cost and infrastructure required. Alternative screening methods have been implemented in such countries such as Visual Inspection with Acetic acid (VIA) but mortality and morbidity remain high. Since 2007, programmes of vaccination against the most oncogenic types of HPV have been rolled out internationally aiming to capture girls, and eventually potentially boys, before they become sexually active. These programmes have been largely successful, with good coverage and low adverse effects reported. Going forward, the vaccine and the advent of effective HPV screening and self testing mean that there needs to be a reorganisation of current cervical screening programmes.

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“…Unlike prophylactic vaccines, therapeutic vaccines enhance the cell-mediated immune response to target and kill infected cells [11, 12]. Currently, however, no HPV18 tumor models are available to evaluate the efficacy of potential immunotherapies against HPV18-associated malignancies.…”

Section: Introductionmentioning

confidence: 99%

Characterization of HPV18 E6-specific T cell responses and establishment of HPV18 E6-expressing tumor model

Yang

Peng

et al. 2017

Vaccine

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Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer, and subsets of anogenital and oropharyngeal cancers. HPV18 is the second most prevalent high-risk HPV type after HPV16. Furthermore, HPV18 is responsible for approximately 12% of cervical squamous cell carcinoma and 37% of cervical adenocarcinoma cases worldwide. In this study, we aimed to characterize the HPV18-E6-specific epitope and establish an HPV18 animal tumor model to evaluate the E6-specific immune response induced by our DNA vaccine. We vaccinated naïve C57BL/6 mice with a prototype DNA vaccine, pcDNA3-HPV18-E6, via intramuscular injection followed by electroporation, and analyzed the E6-specific CD8+ T cell responses by flow cytometry using a reported T cell epitope. We then characterized the MHC restriction element for the characterized HPV18-E6 epitope. Additionally, we generated an HPV18-E6-expressing tumor cell line to study the antitumor effect mediated by E6-specific immunity. We observed a robust HPV18-E6aa67-75 peptide-specific CD8+ T cell response after vaccination with pcDNA3-HPV18-E6. Further characterization demonstrated that this epitope was mainly restricted by H-2Kb, but was also weakly presented by HLA-A*0201, as previously reported. We observed that vaccination with pcDNA3-HPV18-E6 significantly inhibited the growth of HPV18-E6-expressing tumor cells, TC-1/HPV18-E6, in mice. An antibody depletion study demonstrated that both CD4+ and CD8+ T cells are necessary for the observed antitumor immunity. The characterization of HPV18-E6-specific T cell responses and the establishment of HPV18-E6-expressing tumor cell line provide infrastructures for further development of HPV18-E6 targeted immunotherapy.

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Perspectives for therapeutic HPV vaccine development

Cited by 171 publications

References 101 publications

Preparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate

Preparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate

Prevention of Cervical Cancer

Characterization of HPV18 E6-specific T cell responses and establishment of HPV18 E6-expressing tumor model

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