Individual Analysis of Mice Vaccinated against a Weakly Immunogenic Self Tumor-Specific Antigen Reveals a Correlation between CD8 T Cell Response and Antitumor Efficacy

Antonio Rosato, Alessia Zoso, Gabriella Milan, Beatrice Macino, Silvia Dalla Santa, Valeria Tosello, Emma Di Carlo, Piero Musiani, Robert G. Whalen, Paola Zanovello

Research output: Contribution to journalArticle

Abstract

The weakly immunogenic murine P1A Ag is a useful experimental model for the development of new vaccination strategies that could potentially be used against human tumors. An i.m. DNA-based immunization procedure, consisting of three inoculations with the P1A-coding pBKCMV-P1A plasmid at 10-day intervals, resulted in CTL generation in all treated BALB/c mice. Surprisingly, gene gun skin bombardment with the pBKCMV-P1A vector did not induce CTL, nor was it protective against a lethal challenge with the syngeneic P1A-positive J558 tumor cell line. To speed up the immunization procedure, we pretreated the tibialis anterior muscles with cardiotoxin, which induces degeneration of myocytes while sparing immature satellite cells. The high muscle-regenerative activity observable after cardiotoxin inoculation was associated with infiltration of inflammatory cells and expression of proinflammatory cytokines. A single pBKCMV-P1A plasmid inoculation in cardiotoxin-treated BALB/c mice allowed for sustained expansion of P1A-specific CTL and the induction of strong lytic activity in

Original languageEnglish
Pages (from-to)5172-5179
Number of pages8
JournalJournal of Immunology
Volume171
Issue number10
Publication statusPublished - Nov 15 2003

ASJC Scopus subject areas

  • Immunology

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