Vaccination strategies for the treatment and prevention of cervical cancer.
OBJECTIVE
Immunotherapy of HPV-induced premalignant anogenital lesions and cervical cancer has made impressive progress. HPV as causative agent is targeted by prophylactic and therapeutic vaccination strategies. Preclinical and clinical studies have shown induction of natural and/or vaccine-induced immune responses. This review will summarize the status of vaccine development and clinical testing published since March 2003.


RESULTS
For prophylactic vaccines there is first clinical evidence of effectivity (ie, 100% protection from HPV infection and dysplasia by virus-like particle (VLP) vaccine-induced neutralizing antibodies). Also, therapeutic vaccines have entered clinical evaluation. While prophylactic VLP vaccines are immunogenic per se, therapeutic vaccines will need further adjuvants to guide T cell differentiation, expansion, survival, and homing to tumor sites. To enhance clinical outcome of successful T cell induction in patients, the susceptibility of the tumor cells for lysis must be addressed in the future, since tumor immune evasion is a severe problem in cervical cancer.


CONCLUSIONS
While successful prophylactic HPV vaccines have entered large clinical trials, therapeutic HPV vaccines, in spite of T cell induction, lack clinical responses due to the problem of tumor immune evasion. Adjuvants for systemic and local immune modulation will be mandatory for effective therapy.
Schreckenberger
Carola
C
Gynäkologische Molekularbiologie, Frauenklinik, Friedrich-Schiller-Universität Jena, Jena, Germany.
Kaufmann
Andreas M
AM
D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000628:therapy* / Q000821:virology
D019496:Cancer Vaccines