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Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)
Author(s) -
Kaufmann Andreas M.,
Nieland John D.,
Jochmus Ingrid,
Baur Siegfried,
Friese Klaus,
Gabelsberger Joseph,
Gieseking Friederike,
Gissmann Lutz,
Glasschröder Birgit,
Grubert Thomas,
Hillemanns Peter,
Höpfl Reinhard,
Ikenberg Hans,
Schwarz Jörg,
Karrasch Matthias,
Knoll Anette,
Küppers Volkmar,
Lechmann Martin,
Lelle Ralph J.,
Meissner Harald,
Müller Rainer T.,
Pawlita Michael,
Petry Karl Ulrich,
Pilch Henryk,
Walek Elke,
Schneider Achim
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23022
Subject(s) - cervical intraepithelial neoplasia , medicine , vaccination , cervical cancer , hpv vaccines , adverse effect , immunology , placebo , virus , titer , fusion protein , clinical trial , antibody , intraepithelial neoplasia , immune system , virology , immunotherapy , immunization , recombinant dna , cancer , hpv infection , biology , prostate cancer , pathology , biochemistry , alternative medicine , gene
Abstract Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus‐like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus‐like particles (CVLP) consist of a carboxy‐terminally truncated HPV16L1 protein fused to the amino‐terminal part of the HPV16 E7 protein and self‐assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1‐ and E7‐specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo‐controlled clinical trial has been conducted in 39 HPV16 mono‐infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 μg or 250 μg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty‐six percent of the responders were also HPV16 DNA‐negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. © 2007 Wiley‐Liss, Inc.