Enhanced Efficacy of Tumor Cell Vaccines Transfected with Secretable hsp70

Chiara Massa, Cristiana Guiducci, Ivano Arioli, Mariella Parenza, Mario P. Colombo, Cecilia Melani

Research output: Contribution to journalArticle

Abstract

Tumor immunotherapy has exploited the ability of heat shock proteins to chaperone precursors of antigenic peptides to antigen-presenting cells and to activate efficiently an immune response against tumor-associated antigens. The most common strategy is based on the purification of heat shock protein-peptide complexes from tumor cell lines or from tumor surgical samples for in vivo administration. In this article, we have modified the murine-inducible hsp70 into a secreted protein and engineered tumor cells to secrete constitutively their antigenic repertoire associated with the hsp70 protein. In vitro studies showed that the relocalization of hsp70 from the cytoplasm to the secretory pathway did not modify the ability of hsp70 to interact with peptides derived either from natural tumor-associated antigens or model antigens, and that antigen-presenting cells specifically took up the secreted hsp70 and presented the chaperoned epitopes to T cells. In vivo studies showed that tumors secreting hsp70 displayed increased immunogenicity, with induction of a strong and specific CTL response. Mice injected with hsp70-secreting tumors showed increased survival and impaired tumor take compared with mice bearing parental tumors. More than 70% of mice rejected tumor cells secreting hsp70 through mechanisms that involve T lymphocytes and natural killer cells, with the induction of a memory response in the case of T lymphocytes. Moreover, hsp70 secretion increased the immunogenic potential of tumor cell vaccines.

Original languageEnglish
Pages (from-to)1502-1508
Number of pages7
JournalCancer Research
Volume64
Issue number4
DOIs
Publication statusPublished - Feb 15 2004

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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