Epitopes described in "A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions."

Article Authors:Peggy J de Vos van Steenwijk; Tamara H Ramwadhdoebe; Margriet J G Löwik; Caroline E van der Minne; Dorien M A Berends-van der Meer; Lorraine M Fathers; A Rob P M Valentijn; Jaap Oostendorp; Gert Jan Fleuren; Bart W J Hellebrekers; Marij J P Welters; Mariette I van Poelgeest; Cornelis J M Melief; Gemma G Kenter; Sjoerd H van der Burg
Article Title:A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions.
Reference Detail
Reference ID:1025073
Abstract:The aim of this study was to investigate the capacity of an HPV16 E6/E7 synthetic overlapping long-peptide vaccine to stimulate the HPV16-specific T-cell response, to enhance the infiltration of HPV16-specific type 1 T cells into the lesions of patients with HPV16+ high-grade cervical squamous intraepithelial lesion (HSIL) and HPV clearance. This was a placebo-controlled randomized phase II study in patients with HPV16-positive HSIL. HPV16-specific T-cell responses were determined pre- and post-vaccination by ELISPOT, proliferation assay and cytokine assays in PBMC and HSIL-infiltrating lymphocytes, and delayed-type hypersensitivity skin tests. Motivational problems of this patient group to postpone treatment of their premalignant lesions affected the inclusion rates and caused the study to stop prematurely. Of the accrued patients, 4 received a placebo and 5 received 1-2 vaccinations. Side effects mainly were flu-like symptoms and injection site reactions. A strong HPV-specific IFN-associated T-cell response was detected by ELISPOT in all vaccinated patients. The outcome of the skin tests correlated well with the ELISPOT analysis. The cytokine profile associated with HPV16-specific proliferation varied from robust type 1 to dominant type 2 responses. No conclusions could be drawn on vaccine-enhanced T-cell infiltration of the lesion, and there was no HPV clearance at the time of LEEP excision. Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects.
Affiliations:Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands. p.j.de_vos_van_steenwijk@lumc.nl.
Reference Type:Literature
PubMed ID:22684521
Journal:Cancer Immunol Immunother
Journal Volume:61
Article Pages:1485-92
Journal ISSN:0340-7004
Article Chemical List:Cancer Vaccines;E6 protein, Human papillomavirus type 16;Oncogene Proteins, Viral;Papillomavirus E7 Proteins;Papillomavirus Vaccines;Repressor Proteins;oncogene protein E7, Human papillomavirus type 16
Article MeSH List:Cancer Vaccines(immunology; therapeutic use); Cervical Intraepithelial Neoplasia(immunology; therapy; virology); Female; Humans; Hypersensitivity, Delayed(immunology); Oncogene Proteins, Viral(immunology); Papillomaviridae(immunology); Papillomavirus E7 Proteins(immunology); Papillomavirus Infections(immunology; therapy); Papillomavirus Vaccines(immunology; therapeutic use); Repressor Proteins(immunology); T-Lymphocytes(immunology); Uterine Cervical Dysplasia(immunology; therapy); Uterine Cervical Neoplasms(immunology; therapy; virology)
Curation Last Updated:2015-06-07 20:17:28