Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: Synergy with the CD28 co-stimulatory pathway

Ignacio Melero, Nathan Bach, Karl Erik Hellström, Alejandro Aruffo, Robert S. Mittler, Lieping Chen

Research output: Contribution to journalArticle

Abstract

We have explored the role of an activation-induced T cell molecule, 4-1BB (CDw137), in the amplification of tumor immunity by retrovirus-mediated transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte (CTL) response and long-term immunity against wild-type tumor. The optimal effect of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this interaction by antibodies down-regulated the expression of 4-1BB on T cells and decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single transfectants were effective, suggesting a synergistic effect between the 4-1BB and the CD28 co-stimulatory pathways. Our results underscore the importance of the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune response.

Original languageEnglish (US)
Pages (from-to)1116-1121
Number of pages6
JournalEuropean Journal of Immunology
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 1998
Externally publishedYes

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Keywords

  • Co-stimulatory molecule
  • Cytotoxic T lymphocyte
  • Gene therapy
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology

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