Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7-1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity

Hyam I. Levitsky, Jami Montgomery, Mojgan Ahmadzadeh, Kevin Staveley-O'Carroll, Frank Guarnieri, Dan L. Longo, Larry W. Kwak

Research output: Contribution to journalArticle

Abstract

Recently, genetically modified tumor cell vaccines have been described for nonhematopoietic cancers in which the relevant Ags are unknown. Several of these cell-based vaccine strategies have been shown to induce T cell-mediated systemic antitumor immunity, either by enhancing the processing and presentation of tumor Ags by host APCs or by facilitating effective Ag presentation by the tumor vaccine itself. These strategies were compared in a model B cell lymphoma, a tumor derived from APCs, which have the inherent capacity to activate Ag-specific T cells. Eradication of pre-established systemic lymphoma was achieved following immunization with lymphoma cells engineered to produce granulocyte-macrophage (GM)-CSF, and to a lesser extent cells producing IL-4, whereas vaccination with lymphoma cells transfected with the genes encoding IL-2 or B7-1 had no effect. The systemic immunity generated by GM-CSF- or IL-4-transfected lymphoma required both CD4+ and CD8+ T cells. Previous immunotherapeutic strategies for the treatment of lymphoma have focused on the generation of Ab responses targeted to the unique Ig Id as a tumor-specific Ag. Anti-idiotypic Abs were undetectable in animals vaccinated with GM-CSF-transduced lymphoma cells. In contrast, such immunization did result in the induction of Id-specific T cell responses. This is the first demonstration that T cell responses specific for a native tumor Ag are generated by GM-CSF-transduced tumor cell-based vaccination, suggesting that B cell lymphoma may be a suitable disease for genetically modified tumor vaccine strategies.

Original languageEnglish (US)
Pages (from-to)3858-3865
Number of pages8
JournalJournal of Immunology
Volume156
Issue number10
StatePublished - May 15 1996

ASJC Scopus subject areas

  • Immunology

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    Levitsky, H. I., Montgomery, J., Ahmadzadeh, M., Staveley-O'Carroll, K., Guarnieri, F., Longo, D. L., & Kwak, L. W. (1996). Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7-1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity. Journal of Immunology, 156(10), 3858-3865.