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. CONCLUSION: 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.
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-16E7 (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 mousetumor 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. CONCLUSION: 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.
Authors: S C Esparza-González; A Troy; J Troudt; M J Loera-Arias; J Villatoro-Hernández; E Torres-López; J Ancer-Rodríguez; Y Gutiérrez-Puente; G Muñoz-Maldonado; O Saucedo-Cárdenas; R Montes-de-Oca-Luna; A Izzo Journal: Scand J Immunol Date: 2012-03 Impact factor: 3.487
Authors: Larissa H Haut; Amanda L Gill; Raj K Kurupati; Ang Bian; Yan Li; Wynetta Giles-Davis; Zhiquan Xiang; Xiang Yang Zhou; Hildegund C J Ertl Journal: Hum Gene Ther Methods Date: 2016-09-07 Impact factor: 2.396
Authors: Kent A Smith; Brenna L Meisenburg; Victor L Tam; Robb R Pagarigan; Raymond Wong; Diljeet K Joea; Liz Lantzy; Mayra A Carrillo; Todd M Gross; Uriel M Malyankar; Chih-Sheng Chiang; Diane M Da Silva; Thomas M Kündig; W Martin Kast; Zhiyong Qiu; Adrian Bot Journal: Clin Cancer Res Date: 2009-09-29 Impact factor: 12.531