Complement-dependent cytotoxicity of an antibody to melanin in radioimmunotherapy of metastatic melanoma

Thomas Jandl, Ekaterina Revskaya, Zewei Jiang, Ruth A. Bryan, Arturo Casadevall, Ekaterina Dadachova

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Aim: Novel treatments for metastatic melanoma are urgently needed. Materials & 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalImmunotherapy
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2013

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Keywords

  • ADCC
  • CDC
  • antibody-dependent cell-mediated cytotoxicity
  • complement system
  • complement-dependent cytotoxicity
  • immunotherapy
  • melanoma
  • radioimmunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Jandl, T., Revskaya, E., Jiang, Z., Bryan, R. A., Casadevall, A., & Dadachova, E. (2013). Complement-dependent cytotoxicity of an antibody to melanin in radioimmunotherapy of metastatic melanoma. Immunotherapy, 5(4), 357-364. https://doi.org/10.2217/imt.13.16