Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial

Fiander, Alison; Tristram, Amanda; Davidson, Emma; Tomlinson, Anne E; Man, Stephen; Baldwin, P. J.; Sterling, Jane; Kitchener, H.

doi:10.1136/ijgc-00009577-200605000-00020

Cited by 42 publications

(20 citation statements)

References 12 publications

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“…No serious adverse effects were observed in all patients; in addition, 5 out of 29 patients showed increased HPV-16-specific T cell mediated immune responses. However, the result does not show significant advantage over single TA-HPV vaccination [78]. In another prime-boost regimen, ten patients with HPV-16+ high-grade vulvar intraepithelial neoplasia were primed with TA-HPV and boosted with TA-CIN.…”

Section: Protein-based Vaccinesmentioning

confidence: 89%

“…In a Phase I trial, vaccination with TA-CIN was shown to induce antibody responses against L2 in all patients and T cell immunity against HPV-16 E6 and E7 oncoproteins in 8 out of 11 healthy patients receiving the highest dose, proving to be safe and immunogenic [66]. Phase II trials have focused on using TA-CIN as part of a prime-boost regimen with TA-HPV [77][78][79] since preclinical studies suggested this was a more effective regimen [80]. For example, in a Phase II clinical trial, HPV protein-based vaccine, TA-CIN, was used for priming and a recombinant vaccinia virus encoding HPV-16/18, E6/E7 fusion protein (TA-HPV) was used for boosting in 29 patients with anogenital intraepithelial neoplasia.…”

Section: Protein-based Vaccinesmentioning

confidence: 99%

“…Due to the success of prime-boost regimens in preclinical studies, several clinical trials have evaluated the safety and efficacy of these heterologous strategies [77][78][79]. In a Phase II clinical trial, priming with HPV-16 L2/E6/E7 protein (TA-CIN) vaccine was followed by boosting with vaccinia expressing HPV-16/18 E6/E7 (TA-HPV) in women with highgrade anogenital intraepithelial neoplasia (AGIN).…”

Section: A Prime-boost Regimensmentioning

confidence: 99%

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HPV and Therapeutic Vaccines: Where are We in 2010?

Ma¹,

Xu²,

Hung³

et al. 2010

CCTR

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The discovery of human papillomavirus (HPV) as a necessary etiological factor for cervical cancer has spurred the development of preventive and therapeutic HPV vaccines for the control of HPV-associated malignancies including cervical, vulvar, vaginal, and a subset of head and neck cancers. The commercial preventive HPV vaccines, Gardasil and Cervarix, use HPV virus-like particles to generate neutralizing antibodies against HPV major capsid protein L1. However, they do not exert therapeutic effects on existing lesions and are unlikely to have an immediate impact on the prevalence of cervical cancer due to their cost and limited availability in developing countries, which account for more than 80% of cervical cancers. Thus, there is an urgent need for therapeutic HPV vaccines. Therapeutic HPV vaccines can eliminate preexisting lesions and infections by generating cellular immunity against HPV-infected cells. HPV E6 and E7 oncoproteins represent ideal targets for therapeutic intervention because of their constitutive expression in HPV-associated tumors and their crucial role in the induction and maintenance of HPV-associated disease. This review discusses the current progress of various therapeutic HPV vaccine approaches, including live vector-based, peptide/protein-based, nucleic acid-based and cell-based vaccines targeting E6 and/or E7 antigens, and their future prospects for the control of HPV-associated malignancies.

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Section: Protein-based Vaccinesmentioning

confidence: 89%

Section: Protein-based Vaccinesmentioning

confidence: 99%

Section: A Prime-boost Regimensmentioning

confidence: 99%

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HPV and Therapeutic Vaccines: Where are We in 2010?

Ma¹,

Xu²,

Hung³

et al. 2010

CCTR

View full text Add to dashboard Cite

show abstract

“…Due to the enhanced efficacy of the vaccines using a prime-boost regimen in preclinical models, these combinatorial HPV vaccines have entered clinical trials. A clinical trial in patients with anogenital intraepithelial neoplasia demonstrated that a prime-boost regimen consisting of HPV-16 L2/E6/E7 fusion protein (TA-CIN) followed by a recombinant vaccinia virus encoding the E6/ E7 fusion proteins of HPV types-16 and -18 (TA-HPV) could enhance HPV-16 antigen-specific T cell responses which correlated with clinical regression [116,117].…”

Section: Future Directionsmentioning

confidence: 99%

Immunotherapy for head and neck cancer

Niparko

Pai

2008

J Biomed Sci

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Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.

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“…While this primeboost regimen induced cellular immunity in VIN patients, no direct correlation between clinical and immunological responses was seen. Moreover, one of the first randomized Phase II clinical trials of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of anogenital lesions failed to demonstrate any significant advantages of the prime-boost approach over single TA-HPV vaccination [131].…”

Section: Prime-boost Strategymentioning

confidence: 99%

Human papillomavirus therapeutic vaccines in head and neck tumors

Badaracco

Venuti

2007

Expert Review of Anticancer Therapy

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Head and neck cancer represents one of the most challenging diseases as the mortality remains high despite advances in early diagnosis and treatment. Human papillomavirus has been implicated in a third of head and neck squamous cell carcinomas and human papillomavirus type 16 is strongly associated with carcinomas arising from the oropharynx, the tonsil being the preferred infected site. Novel therapeutic approaches including immunotherapy are currently under investigation. Immune vaccines developed against human papillomavirus in the genital area are already available and could simultaneously protect other anatomical localizations; however, prophylactic vaccines are expected to be effective in reducing the incidence of tumors after many years and, therefore, there is an urgent need to improve therapeutic interventions, such as immunotherapy. To date, human papillomavirus therapeutic vaccines are either at the preclinical level or at early phase human trials for genital pathologies. Nevertheless, accumulating evidence from animal and clinical studies suggests that the enhancement of specific and innate immune responses is effective in clearance of the human papillomavirus infection, promoting a cautious optimism regarding the achievement of an efficacious immunotherapy. This article reviews what has been achieved and what remains to be done in the field for the development of future viral vaccines in head and neck tumors.

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Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial

Cited by 42 publications

References 12 publications

HPV and Therapeutic Vaccines: Where are We in 2010?

HPV and Therapeutic Vaccines: Where are We in 2010?

Immunotherapy for head and neck cancer

Human papillomavirus therapeutic vaccines in head and neck tumors

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