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The 4-1BB (CDw137) T-cell molecule is a member of the TNF receptor family and triggering by either 4-1BB ligand or antibody ligation induces T-cell activation and growth. We have recently demonstrated that administration of anti-4-1BB monoclonal antibodies (mAb) induced the regression of established large tumors in several mouse models by activation of T-cell-mediated immunity. Herein we report that selective depletion of natural killer (NK) cells in mice by the anti-AsialoGM1 or anti-NK1.1 antibodies completely abrogated the antitumor effect of anti-4-1BB mAb. However, it is unlikely that NK1. 1 cells are the effectors of the response because P815 cells are resistant to lysis by NK1.1 cells in vitro. Despite the fact that activated NK1.1 cells express 4-1BB on their surface, redirection of NK1.1 cells by anti-4-1BB mAb or by transfection into P815 cells of the 4-1BB natural ligand did not trigger cytolysis. Our results thus gain further insight into the cellular mechanisms of the antitumor effects of anti-4-1BB mAb and implicate an immunoregulatory rather than effector function of 4-1BB molecule on NK1.1 cells.

Original publication




Journal article


Cellular immunology

Publication Date





167 - 172


Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington, 98121, USA.


Killer Cells, Natural, Tumor Cells, Cultured, Animals, Mice, Inbred C57BL, Humans, Mice, Neoplasms, Proteins, Lectins, C-Type, Receptors, Tumor Necrosis Factor, Receptors, Nerve Growth Factor, Antigens, CD, Antigens, Ly, Antibodies, Monoclonal, Antigens, Antigens, Surface, NK Cell Lectin-Like Receptor Subfamily B, Tumor Necrosis Factor Receptor Superfamily, Member 9