world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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Fig. 4.23 Proteins which make up the HPV particle<br />
are used in the manufacture of a vaccine.<br />
Fig. 4.24 Collecting blood from a participant in an<br />
HPV prevalence study, Ibadan, Nigeria.<br />
regression of HPV-associated lesions. The<br />
E6 and E7 proteins (Oncogenes and<br />
tumour suppressor genes, p96) are the<br />
natural targets for these vaccines because<br />
such proteins are consistently expressed<br />
in cervical <strong>cancer</strong> cells. Since neither protein<br />
is located on the cell surface, the<br />
most effective mechanism for the<br />
destruction of <strong>cancer</strong> cells is likely to be<br />
through the action of cytotoxic T cells<br />
which recognize intracellular processed<br />
peptides in complex with major histocompatibility<br />
complex (MHC) class I molecules.<br />
Candidate therapeutic vaccines are<br />
constituted using either synthetic peptides,<br />
recombinant proteins or live vectors<br />
coding for HPV proteins [8].<br />
Several vaccines that target the E6 and E7<br />
oncoproteins of HPV 16 and 18 are now<br />
available and are being used in phase I-II<br />
trials (Table 4.11). These trials have been,<br />
or are being carried out in patients with<br />
advanced cervical <strong>cancer</strong> or in patients<br />
with genital pre<strong>cancer</strong>ous lesions. Some<br />
of the vaccines are peptide-based while<br />
others are based on a recombinant vaccinia<br />
vector expressing E6 and E7 from<br />
both HPV 16 and 18 [9]. Results from only<br />
one of these trials have been published in<br />
full [10]. As is the case for prophylactic<br />
HPV vaccines, in order to develop safe and<br />
Organization HPV type and Vaccine type Current status<br />
(vaccine name) antigen<br />
Medimmune SmithKline HPV-11 L1 VLP Phase II trials under way;<br />
Beecham safety and immune<br />
(MEDI-501) response proven in<br />
Phase I trials<br />
Medimmune SmithKline HPV-16, 18 L1 VLP Phase II trials under way<br />
Beecham<br />
(MEDI-503, 504)<br />
Merck, CSL Limited HPV-16 L1 VLP Phase II trials under way<br />
in USA, UK and Australia;<br />
Phase III to begin soon<br />
National Cancer Institute, HPV-16 L1 VLP Phase II trials under way;<br />
NIAID large-scale efficacy trial<br />
planned to begin in<br />
Costa Rica in 2002<br />
Medigene HPV16 L1, E7 VLP Phase I/II trial<br />
Table 4.9 Prophylactic HPV vaccines under development in clinical trials. VLP = virus-like particles<br />
effective therapeutic vaccines, serious<br />
technical difficulties must be overcome.<br />
Such vaccines must be tailored to the<br />
MHC antigens of the recipients and must<br />
elicit a stronger anti-tumour response<br />
than that produced without vaccination.<br />
Combined or chimeric vaccines are<br />
designed to have the ability to both protect<br />
against HPV infection and induce<br />
regression of HPV-associated lesions [8].<br />
The first approach considered was to<br />
develop an L1 or L1-L2 VLP-based vaccine<br />
capable of inducing a cytotoxic T-cell<br />
response. Another approach being used is<br />
the production of chimeric VLPs that con-<br />
Issue Comments<br />
Table 4.10 Open issues in the development of prophylactic HPV vaccines.<br />
tains both L1 or L1-L2 and E6 or E7 proteins<br />
[9]. Such vaccines should induce a<br />
protective response elicited by L1 or L2<br />
proteins and a cytotoxic T cell-mediated<br />
response elicited by the E6 or E7 proteins.<br />
There are still many technical and practical<br />
problems to be solved before safe,<br />
effective and inexpensive HPV vaccines<br />
are produced for mass use in the general<br />
population. Although these problems<br />
appear to be greater for therapeutic vaccines,<br />
their production has moved into an<br />
industrial phase. Lessons learnt from the<br />
slow introduction of hepatitis B virus vaccine<br />
into routine immunization pro-<br />
HPV types to be included At least 30 oncogenic types exist, but HPV 16<br />
accounts for 50% and HPV 18, 31, and 45 together for<br />
a further 30% of cervical <strong>cancer</strong>s<br />
Route of administration Oral or nasal spray<br />
Target population Ideally infants, girls and boys<br />
Cost It should be low, perhaps using bacterial vectors or<br />
transgenic plants<br />
Human papillomavirus vaccination 149