Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors
| Autor: | Ignacio Melero, Karl Erik Hellström, Robert S. Mittler, Lieping Chen, Alejandro Aruffo, Walter W. Shuford, Stephanie Ashe Newby, Jeffrey A. Ledbetter |
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| Rok vydání: | 1997 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.drug_class medicine.medical_treatment T cell Mast-Cell Sarcoma Receptors Nerve Growth Factor Biology CD8-Positive T-Lymphocytes Monoclonal antibody General Biochemistry Genetics and Molecular Biology Receptors Tumor Necrosis Factor chemistry.chemical_compound Mice Tumor Necrosis Factor Receptor Superfamily Member 9 Immune system Antigen Antigens CD medicine Tumor Cells Cultured Animals Mice Inbred C3H CD137 Antibodies Monoclonal General Medicine Immunotherapy Molecular biology 4-1BB ligand medicine.anatomical_structure chemistry Mice Inbred DBA Female Sarcoma Experimental CD8 Neoplasm Transplantation T-Lymphocytes Cytotoxic |
| Zdroj: | Nature medicine. 3(6) |
| ISSN: | 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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