Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mice.
Despite promising preclinical results of various therapeutic anticancer immunization strategies, these approaches may not be effective enough to eradicate tumors in cancer patients. While most animal models are based on fast-growing transplantable tumors, malignancies in, for example, cervical cancer patients in general develop much more slowly, which may lead to immune suppression and/or immune tolerance. As a consequence, the immunomodulating signal of any therapeutic immunization regimen should be sufficiently potent to overcome this immunocompromised condition. In previous studies, we demonstrated that an experimental vaccine against human papillomavirus (HPV)-induced cervical cancer, based on Semliki Forest virus (SFV), induces robust HPV-specific cellular immune responses in mice. Now we studied whether this strategy is potent enough to also prime a cellular immune response in immune-tolerant HPV transgenic mice, in which CTL activity cannot be induced using protein or DNA vaccines. We demonstrate that, depending on the route of immunization, SFV-expressing HPV16 E6 and E7 indeed has the capacity to induce HPV16 E7-specific cytotoxic T cells in HPV-transgenic mice.
Riezebos-Brilman
A
A
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen (UMCG), Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Regts
J
J
Freyschmidt
E-J
EJ
Dontje
B
B
Wilschut
J
J
Daemen
T
T
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy*; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000628:therapy*
D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16