title: Complement-dependent cytotoxicity of an antibody to melanin in radioimmunotherapy of metastatic melanoma.
abstract: OBJECTIVE
  Novel treatments for metastatic melanoma are urgently needed.
  
  
  METHODS
  We developed radioimmunotherapy of metastatic melanoma using 6D2 monoclonal antibody (mAb) to melanin with encouraging therapeutic results, preclinically and in patients.
  
  
  RESULTS
  We observed tumor suppression with the unlabeled 6D2 mAb and investigated its tumoricidal mechanisms. In melanoma tumor-bearing mice, we detected more complement-C3 deposition in the tumors from 188-rhenium-labeled 6D2 mAb-treated mice when compared with untreated controls. 6D2 and isotype-control mAb TEPC caused suppression of tumor growth in A2058 melanoma tumor-bearing mice. Tumors of mice treated with the unlabeled 6D2 mAb were infiltrated with more lymphocytes compared with controls. In vitro antibody-dependent cell-mediated cytotoxicity did not contribute to the tumor-suppressive effect of 6D2 mAb, while 6D2 mAb demonstrated a strong effect on initiating complement-dependent cytotoxicity.
  
  
  CONCLUSIONS
  We concluded that 6D2 mAb mediated complement-dependent cytotoxicity, resulting in killing of the tumor cells and suppression of tumor growth. These observations will help to improve the treatment protocols of radioimmunotherapy, as well as immunotherapy.
authors.affiliation: Department of Radiology, Albert Einstein College of Medicine, 1695A Eastchester Road, Bronx, NY 10461, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jandl
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Revskaya
authors.forename: Zewei
authors.initials: Z
authors.lastname: Jiang
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Bryan
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D015153:Blotting, Western; D003176:Complement C3 / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D008543:Melanins / Q000276:immunology*; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D016499:Radioimmunotherapy; D012211:Rhenium
chemical_list: D000911:Antibodies, Monoclonal; D003176:Complement C3; D008543:Melanins; D012211:Rhenium