Anti-GD3 monoclonal antibody effects on lymphocytes and antibody-dependent cellular cytotoxicity

Pierre L. Triozzi, Jatin J. Shah, Wen Quan Wang, Wayne Aldrich, Jeffrey C. Edberg, Kaihong Su, Ronda Carlisle, Robert Conry, Albert F. LoBuglio, Andres Forero

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Purpose: Antibodies targeting GD3 gangliosides highly expressed on melanomas mediate immune effector functions in vitro and inhibit animal model melanoma tumor growth in vivo. Because GD3 is expressed also on a subpopulation of human lymphocytes, we characterized the in vitro immune effects of murine R24 and a chimeric anti-GD3 antibody (KW-2871). Design: Anti-GD3 complement-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested against cell line Mel-624. Antibody-mediated lymphocyte expression of interleukin (IL)-2, 1L-4, IL-10, and interferon-γ (IFN-γ) was quantified. The effect of antibody and antibody-treated lymphocyte supernates on effector cell ADCC and Fc receptor expression were evaluated. Results: R24 and KW-2871 antibodies mediated CMC and ADCC to the Mel-624 cell line. R24 induced potent lymphocyte proliferation and enhanced lymphocyte RNA expression of IL-4 (2-4 logs), IL-10, and IFN-γ (> 10-fold). KW-2871 induced no lymphocyte proliferation and had minimal effects on lymphokine expression (< 5-fold). Preincubation of effector cells with either antibody inhibited ADCC and reduced monocyte expression of FcγRI and H. Supernates of effector cells preincubated with either antibody were able to inhibit ADCC. Conclusions: R24 and KW-2871 antibody differ in their lymphocyte proliferation and lymphokine release activity but have similar inhibition of lymphocyte ADCC and FcyR expression in vitro.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalCancer Biotherapy and Radiopharmaceuticals
Volume21
Issue number6
DOIs
Publication statusPublished - Dec 1 2006

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Keywords

  • ADCC
  • GD3 monoclonal antibody
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Triozzi, P. L., Shah, J. J., Wang, W. Q., Aldrich, W., Edberg, J. C., Su, K., ... Forero, A. (2006). Anti-GD3 monoclonal antibody effects on lymphocytes and antibody-dependent cellular cytotoxicity. Cancer Biotherapy and Radiopharmaceuticals, 21(6), 553-560. https://doi.org/10.1089/cbr.2006.21.553