CTL response and protection against P815 tumor challenge in mice immunized with DNA expressing the tumor-specific antigen P815A

Antonio Rosato, Annalisa Zambon, Gabriella Milan, Vincenzo Ciminale, Donna M. D'Agostino, Beatrice Macino, Paola Zanovello, Dino Collavo

Research output: Contribution to journalArticlepeer-review

Abstract

A DNA immunization approach was used to induce an immune response against the tumor-specific antigen P815A in DBA/2 mice. The PIA gene, which encodes the P815A antigen, was modified by the addition of a short sequence coding for a tag epitope recognized by the monoclonal antibody AU1, and cloned into the eukaryotic expression vector pBKCMV, resulting in plasmid pBKCMV-P1A. L1210 cells stably transfected with pBKCMV-P1A expressed P1A mRNA and were lysed by the syngeneic P815A-specific cytotoxic clone CTL-P1:5, thus confirming that the tag-modified P1A protein underwent correct processing and presentation. A single intramuscular injection of 100 μg of pBKCMV-P1A induced the expression of P1A mRNA for at least 4 months. Eighty percent of DBA/2 mice injected three times with 100 μg of pBKCMV-P1A generated cytotoxic T lymphocytes (CTL) that lysed P815 tumor cells, whereas mock-inoculated animals failed to show any cytotoxicity. Moreover, experiments designed to evaluate the protection of pBKCMV-P1A-immunized mice against a lethal challenge with P815 tumor cells showed that 6 of 10 immunized mice rejected the tumor, and 2 mice showed prolonged survival compared to control animals.

Original languageEnglish
Pages (from-to)1451-1458
Number of pages8
JournalHuman Gene Therapy
Volume8
Issue number12
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Genetics

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