Zusammenfassung
Aufgrund epidemiologisch/klinischer Beobachtungen und tierexperimenteller Befunde
ist zu erwarten, dass eine HPV-spezifische Immunisierung zur Verhinderung des Zervixkarzinoms
sowohl als Immunprophylaxe durch Induktion neutralisierender Antikörper als auch als
therapeutische Immunisierung (Induktion zytotoxischer T-Zellen bei Frauen mit CIN)
denkbar ist. Eine Immuntherapie von bereits bestehenden Karzinomen ist wahrscheinlich
nur als adjuvante Maßnahme möglich. Als prophylaktische Impfstoffe werden virus-like particles (VLP) entwickelt, die sich durch Expression des L1 Proteins in rekombinanten Systemen
herstellen lassen. Zur Immuntherapie kommen in erster Linie die viralen Onkoproteine
E6 und E7 in Frage, die entweder in gereinigter Form oder mit Hilfe rekombinanter
Vektoren (z. B. Vakzinia Virus) appliziert werden. Erste klinische Studien mit den
häufigsten beim Zervixkarzinom gefundenen HPV-Typen (HPV 16 und 18) zeigen vielversprechende
Ergebnisse, wenn auch bereits heute Impfstoffe der nächsten Generation entwickelt
werden.
Immunization against HPV-infection in the prevention of cervical cancer
Summary
According to epidemiologic and clinical observations as well as from animal experiments
it is expected that prevention of cervical cancer based upon an HPV-specific immunization
can be achieved by prophylactic vaccination (induction of neutralizing antibodies)
or by immune therapy (induction of cytotoxic T cells in women with CIN). Immune therapy
of already existing tumors is most likely only possible as an adjuvant treatment.
Virus-like particles (VLP) are currently being developed as prophylactic vaccine that
can be obtained by expression of the L1 protein. The viral oncoproteins E6 and E7
are prime candidates for therapeutic vaccines administered either as purified molecules
or carried by recombinant vectors such as vaccinia virus. Initial clinical trials
with the HPV types which are most prevalent in cervical cancer exhibited promising
results, yet next generation vaccines are already under development.
Schlüsselwörter
Humapathogene Papillomviren (HPV) - Prophylaxe - Immuntherapie - virus-like particles
(VLP) - klinische Studien
Key words
Human papillomaviruses (HPV) - prophylaxis - immune therapy - virus-like particles
(VLP) - clinical trials
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Prof. Dr. med. Lutz Gissmann
Deutsches Krebsforschungszentrum
Forschungsschwerpunkt Angewandte Tumorvirologie
Im Neuenheimer Feld 242
D-69120 Heidelberg
Telefon: Tel.: 0 62 21/42 46 03
eMail: E-mail: L.Gissmann@dkfz.de