Cancer gene therapy by DNA immunization

Antonio Rosato, Annalisa Zambon, Gabriella Milan, Beatrice Macino, Luigi Quintieri, Paola Zanovello, Dino Collavo

Research output: Contribution to journalArticlepeer-review

Abstract

We are evaluating the possibility of eliciting an immune response against tumors by a DNA-based immunization approach using two experimental models: neoplasias induced by the retroviral complex Moloney-Murine Sarcoma/Leukemia Virus (M-MSV/M-MuLV), and the tumor-specific antigen P815A. Intramuscular injection of young adult mice with M-MSV/M-MuLV retroviral complex gives rise to sarcomas that develop at the inoculation site after a short latency period, and regress spontaneously following the induction of a strong immune reaction, which is mediated mainly by cytotoxic T lymphocytes (CTL) specific for viral antigens. Thus, in this experimental model, virus antigens behave as tumor-specific antigens. P815A antigen is coded by the normal murine gene P1A, and has been shown to represent a major tumor rejection antigen in the mastocytoma cell line P815, derived from a methylcholanthrene-treated DBA/2 mouse. The PIA, gene is expressed in several murine tumors of different histotypes, but remains silent in normal DBA/2 mouse tissues with the exception of testis and placenta. Thus, P815A antigen shares characteristics with human antigens of the MAGE, GAGE and BAGE families, and constitutes a valid model to develop vaccination strategies applicable to human cancers. Results obtained thus far demonstrate that DNA immunization of mice with plasmids encoding env and gag structural proteins of the M-MSV/M-MuLV retroviral complex or P1A induces CTL generation and confers protection against a lethal challenge with tumor cells bearing the relevant antigens.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalMinerva Biotecnologica
Volume9
Issue number4
Publication statusPublished - Dec 1997

Keywords

  • Gene therapy
  • Neoplasms therapy

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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