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

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 intra...

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Main Authors:	de Vos van Steenwijk, Peggy J., Ramwadhdoebe, Tamara H., Löwik, Margriet J. G., van der Minne, Caroline E., Berends-van der Meer, Dorien M. A., Fathers, Lorraine M., Valentijn, A. Rob P. M., Oostendorp, Jaap, Fleuren, Gert Jan, Hellebrekers, Bart W. J., Welters, Marij J. P., van Poelgeest, Mariette I., Melief, Cornelis J. M., Kenter, Gemma G., van der Burg, Sjoerd H.
Format:	Online
Language:	English
Published:	Springer-Verlag 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427705/

id	pubmed-3427705
recordtype	oai_dc
spelling	pubmed-34277052012-08-30 A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions de Vos van Steenwijk, Peggy J. Ramwadhdoebe, Tamara H. Löwik, Margriet J. G. van der Minne, Caroline E. Berends-van der Meer, Dorien M. A. Fathers, Lorraine M. Valentijn, A. Rob P. M. Oostendorp, Jaap Fleuren, Gert Jan Hellebrekers, Bart W. J. Welters, Marij J. P. van Poelgeest, Mariette I. Melief, Cornelis J. M. Kenter, Gemma G. van der Burg, Sjoerd H. Short Communication 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 IFNγ-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. Springer-Verlag 2012-06-09 2012-09 /pmc/articles/PMC3427705/ /pubmed/22684521 http://dx.doi.org/10.1007/s00262-012-1292-7 Text en © The Author(s) 2012
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	de Vos van Steenwijk, Peggy J. Ramwadhdoebe, Tamara H. Löwik, Margriet J. G. van der Minne, Caroline E. Berends-van der Meer, Dorien M. A. Fathers, Lorraine M. Valentijn, A. Rob P. M. Oostendorp, Jaap Fleuren, Gert Jan Hellebrekers, Bart W. J. Welters, Marij J. P. van Poelgeest, Mariette I. Melief, Cornelis J. M. Kenter, Gemma G. van der Burg, Sjoerd H.
spellingShingle	de Vos van Steenwijk, Peggy J. Ramwadhdoebe, Tamara H. Löwik, Margriet J. G. van der Minne, Caroline E. Berends-van der Meer, Dorien M. A. Fathers, Lorraine M. Valentijn, A. Rob P. M. Oostendorp, Jaap Fleuren, Gert Jan Hellebrekers, Bart W. J. Welters, Marij J. P. van Poelgeest, Mariette I. Melief, Cornelis J. M. Kenter, Gemma G. van der Burg, Sjoerd H. A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
author_facet	de Vos van Steenwijk, Peggy J. Ramwadhdoebe, Tamara H. Löwik, Margriet J. G. van der Minne, Caroline E. Berends-van der Meer, Dorien M. A. Fathers, Lorraine M. Valentijn, A. Rob P. M. Oostendorp, Jaap Fleuren, Gert Jan Hellebrekers, Bart W. J. Welters, Marij J. P. van Poelgeest, Mariette I. Melief, Cornelis J. M. Kenter, Gemma G. van der Burg, Sjoerd H.
author_sort	de Vos van Steenwijk, Peggy J.
title	A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
title_short	A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
title_full	A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
title_fullStr	A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
title_full_unstemmed	A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
title_sort	placebo-controlled randomized hpv16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
description	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 IFNγ-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.
publisher	Springer-Verlag
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427705/
_version_	1611552227144499200

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

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