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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 publication




Journal article


European journal of immunology

Publication Date





1116 - 1121


Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, USA.


CD4-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Animals, Mice, Inbred C3H, Mice, Inbred DBA, Mice, Neoplasms, Experimental, Receptors, Tumor Necrosis Factor, Receptors, Nerve Growth Factor, Antigens, CD, Antigens, Neoplasm, Gene Transfer Techniques, Lymphocyte Activation, Cytotoxicity, Immunologic, CD28 Antigens, Tumor Necrosis Factor Receptor Superfamily, Member 9