Effective Genetic Vaccination with a Widely Shared Endogenous Retroviral Tumor Antigen Requires CD40 Stimulation during Tumor Rejection Phase

Vincenzo Bronte, Sara Cingarlini, Elisa Apolloni, Paolo Serafini, Ilaria Marigo, Carmela De Santo, Beatrice Macino, Oriano Marin, Paola Zanovello

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8+, but not CD4+, T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8+ T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8 + T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.

Original languageEnglish (US)
Pages (from-to)6396-6405
Number of pages10
JournalJournal of Immunology
Volume171
Issue number12
DOIs
StatePublished - Dec 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Effective Genetic Vaccination with a Widely Shared Endogenous Retroviral Tumor Antigen Requires CD40 Stimulation during Tumor Rejection Phase'. Together they form a unique fingerprint.

Cite this