HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial

Autor: Edith M.G. van Esch, Margriet J. G. Löwik, Gijs Kerpershoek, Linda F. M. Stynenbosch, Mariette I.E. van Poelgeest, A. Rob P. M. Valentijn, Cornelis J. M. Melief, Dorien M A Berends-van der Meer, Gert Jan Fleuren, Muriel van den Hende, Els L. van Persijn van Meerten, Gemma G. Kenter, Lorraine M. Fathers, Sjoerd H. van der Burg, Jaap Oostendorp, Marij J. P. Welters
Přispěvatelé: Obstetrics and gynaecology, CCA - Innovative therapy
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Journal of Translational Medicine, 11
Journal of Translational Medicine, 11:88. BioMed Central
van Poelgeest, M I, Welters, M J, van Esch, E M, Stynenbosch, L F, Kerpershoek, G, van Persijn-van Meerten, E L, van den Hende, M, Lowik, M J, Berends-van Meer, D M, Fathers, L M, Valentijn, A R, Oostendorp, J, Fleuren, G J, Melief, C J, Kenter, G G & van der Burg, S H 2013, ' HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial ', Journal of Translational Medicine, vol. 11, 88 . https://doi.org/10.1186/1479-5876-11-88
Journal of Translational Medicine
ISSN: 1479-5876
Popis: Background Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Methods Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. Results No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient’s immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. Conclusions The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.
Databáze: OpenAIRE
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