Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice.
BACKGROUND
Cervical cancer remains a leading cause of cancer-related mortality in women, particularly in developing countries. The causal association between genital human papilloma virus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Vaccines targeting the oncogenic proteins, E6 and E7 of HPV-16 and -18 are the focus of current vaccine development. Previous studies have shown that calreticulin (CRT) enhances the MHC class I presentation of linked peptide/protein and may serve as an effective vaccination strategy for antigen-specific cancer treatment.


METHODS
Two replication-deficient adenoviruses, one expressing HPV-16 E7 (Ad-E7) and the other expressing CRT linked to E7 (Ad-CRT/E7), were assessed for their ability to induce cellular immune response and tested for prophylactic and therapeutic effects in an E7-expressing mouse tumor model.


RESULTS
Vaccination with Ad-CRT/E7 led to a dramatic increase in E7-specific T cell proliferation, interferon (IFN)-gamma-secretion, and cytotoxic activity. Immunization of mice with Ad-CRT/E7 was effective in preventing E7-expressing tumor growth, as well as eradicating established tumors with long-term immunological memory.


CONCLUSIONS
Vaccination with an adenoviral vector expressing CRT-E7 fusion protein represents an effective strategy for immunotherapy of cervical cancer in rodents, with possible therapeutic potential in clinical settings.
Gomez-Gutierrez
Jorge G
JG
Department of Surgery, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, KY 40292, USA.
Elpek
Kutlu G
KG
Montes de Oca-Luna
Roberto
R
Shirwan
Haval
H
Sam Zhou
H
H
McMasters
Kelly M
KM
D000256:Adenoviridae; D000818:Animals; D037282:Calreticulin / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
D037282:Calreticulin; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma