Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein.
Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Felicia
F
Grasso
Donatella R M
DR
Negri
Stefania
S
Mochi
Alessandra
A
Rossi
Armando
A
Cesolini
Andrea
A
Giovannelli
Maria Vincenza
MV
Chiantore
Pasqualina
P
Leone
Colomba
C
Giorgi
Andrea
A
Cara
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D037282:Calreticulin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D019426:Integrases / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016086:Lentivirus / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays
D037282:Calreticulin; D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma; D019426:Integrases