Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors

Nat Med. 1997 Jun;3(6):682-5. doi: 10.1038/nm0697-682.


The 4-1BB glycoprotein is a member of the tumor necrosis factor receptor superfamily and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. Expression of 4-1BB is restricted to primed CD4+ and CD8+ T cells, and 4-1BB signaling either by binding to 4-1BBL or by antibody ligation delivers a dual mitogenic signal for T-cell activation and growth. These observations suggest an important role for 4-1BB in the amplification of T cell-mediated immune responses. We now show that administration of anti-4-1BB monoclonal antibodies can eradicate established large tumors in mice, including the poorly immunogenic Ag104A sarcoma and the highly tumorigenic P815 masto cytoma. The immune response induced by anti-4- 1BB monoclonal antibodies is mediated by both CD8+ and CD4+ T cells and is accompanied by a marked augmentation of tumor-selective cytolytic T-cell activity. Our data suggest that a similar approach may be efficacious for immunotherapy of human cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Mast-Cell Sarcoma / immunology
  • Mast-Cell Sarcoma / therapy*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred DBA
  • Neoplasm Transplantation
  • Receptors, Nerve Growth Factor / immunology*
  • Receptors, Tumor Necrosis Factor / immunology*
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / therapy*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antibodies, Monoclonal
  • Antigens, CD
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • Tnfrsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9