Premium
Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein
Author(s) -
Grasso Felicia,
Negri Donatella R.M.,
Mochi Stefania,
Rossi Alessandra,
Cesolini Armando,
Giovannelli Andrea,
Chiantore Maria Vincenza,
Leone Pasqualina,
Giorgi Colomba,
Cara Andrea
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27676
Subject(s) - vaccination , virology , viral vector , integrase , medicine , antigen , immunotherapy , immunology , immunization , cancer , vector (molecular biology) , cervical cancer , cancer research , biology , immune system , human immunodeficiency virus (hiv) , gene , recombinant dna , genetics
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.