title: Enhanced suppression of melanoma tumor growth and metastasis by combined therapy with anti-VEGF receptor and anti-TYRP-1/gp75 monoclonal antibodies.
abstract: Targeted immunotherapy against tumors or angiogenesis has shown promise as an alternative approach for the treatment of malignant disease. Whether or not combining these two treatment modalities would enhance the antitumor effect was tested in mouse models of malignant melanoma. C57BL/6 mice bearing established subcutaneous B16 tumors were treated with anti-vascular endothelial growth factor receptor (anti-VEGFR) fetal liver kinase-1 (Flk-1) monoclonal antibody (mAb) DC101 and/or anti-TYRP-1/gp75 (tyrosinase-related protein-1) mAb TA99. The growth of subcutaneous B16 tumors was significantly suppressed by the mAb DC101 (63%, p<0.001) and by mAb TA99 (75%, p<0.001) treatment alone. The combined antibody (TA99+DC101) treatment resulted in a significant enhancement (93%, p<0.001) of tumor growth suppression. In a B16 pulmonary metastasis model, combined therapy with mAb DC101 and mAb TA99 resulted in a significant reduction of lung metastases compared to the control (p<0.001) and the single agent treatment groups (p<0.05). A combined modality approach that provides passive immunity to melanoma differentiation antigens as well as inhibiting tumor neovascularization may be valuable for the treatment of malignant melanoma.
authors.affiliation: Department of Experimental Therapeutics and Protein Science, ImClone Systems Incorporated, New York, NY 10014, USA.
authors.forename: Dipa
authors.initials: D
authors.lastname: Patel
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bassi
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Hooper
authors.forename: Haijun
authors.initials: H
authors.lastname: Sun
authors.forename: James
authors.initials: J
authors.lastname: Huber
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hicklin
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Kang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D010088:Oxidoreductases / Q000276:immunology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C511761:DC101 monoclonal antibody; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D040262:Receptors, Vascular Endothelial Growth Factor