Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein

Felicia Grasso; Donatella R M Negri; Stefania Mochi; Alessandra Rossi; Armando Cesolini; Andrea Giovannelli; Maria Vincenza Chiantore; Pasqualina Leone; Colomba Giorgi; Andrea Cara

doi:10.1002/ijc.27676

Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein

Int J Cancer. 2013 Jan 15;132(2):335-44. doi: 10.1002/ijc.27676. Epub 2012 Jun 28.

Authors

Felicia Grasso¹, Donatella R M Negri, Stefania Mochi, Alessandra Rossi, Armando Cesolini, Andrea Giovannelli, Maria Vincenza Chiantore, Pasqualina Leone, Colomba Giorgi, Andrea Cara

Affiliation

¹ Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.

PMID: 22700466
DOI: 10.1002/ijc.27676

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / virology
Calreticulin / biosynthesis
Calreticulin / genetics
Calreticulin / immunology
Cancer Vaccines / administration & dosage*
Cancer Vaccines / therapeutic use
Cell Line, Tumor
Female
Gene Expression
Genetic Vectors
Humans
Immunity, Cellular
Immunity, Humoral
Integrases / genetics*
Interferon-gamma / metabolism
Kaplan-Meier Estimate
Lentivirus / enzymology
Lentivirus / genetics*
Mice
Mice, Inbred C57BL
Papillomavirus E7 Proteins / biosynthesis
Papillomavirus E7 Proteins / genetics*
Papillomavirus E7 Proteins / immunology
Papillomavirus Infections / immunology
Papillomavirus Infections / pathology
Papillomavirus Infections / prevention & control*
Papillomavirus Infections / virology
Recombinant Fusion Proteins / biosynthesis
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Tumor Burden
Uterine Cervical Neoplasms / immunology
Uterine Cervical Neoplasms / pathology
Uterine Cervical Neoplasms / prevention & control*
Uterine Cervical Neoplasms / virology
Vaccination
Xenograft Model Antitumor Assays

Substances

Calreticulin
Cancer Vaccines
Papillomavirus E7 Proteins
Recombinant Fusion Proteins
oncogene protein E7, Human papillomavirus type 16
Interferon-gamma
Integrases