1. Int J Cancer. 2007 Dec 15;121(12):2794-800.
Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women
suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).
Kaufmann AM(1), Nieland JD, Jochmus I, Baur S, Friese K, Gabelsberger J,
Gieseking F, Gissmann L, Glasschröder B, Grubert T, Hillemanns P, Höpfl R,
Ikenberg H, Schwarz J, Karrasch M, Knoll A, Küppers V, Lechmann M, Lelle RJ,
Meissner H, Müller RT, Pawlita M, Petry KU, Pilch H, Walek E, Schneider A.
Author information:
(1)Klinik für Frauenheilkunde und Geburtshilfe, Friedrich-Schiller-Universität,
Bachstrasse 18, 07740 Jena, Germany.
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 mug or 250 mug) 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.
(c) 2007 Wiley-Liss, Inc.
PMID: 17721997 [PubMed - indexed for MEDLINE]
