Combination immunotherapy with anti-CD20 and anti-HLA-DR monoclonal antibodies induces synergistic anti-lymphoma effects in human lymphoma cell lines

Evan Tobin, Gerald L Denardo, Nan Zhang, Alan L. Epstein, Cathy Liu, Sally DeNardo

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Rituximab is effective in about one half of patients with indolent lymphoma. Even these patients relapse and develop rituximab resistance. To increase potency and circumvent resistance, the anti-lymphoma effects of rituximab, an anti-CD20 MAb, combined with chLym-1, an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC and CDC. There were additive effects in all assays and synergism in cell lines, such as B35M, which displayed resistance to either MAb alone. In B35M cells, combined rituximab and chLym-1 induced a 27-fold direct reduction in viable cells, whereas equivalent concentrations of rituximab or chLym-1 alone induced only a 1-fold and 10-fold reduction in viable cells, respectively. Because these results occurred at MAb concentrations readily achievable in patients, they suggest that this combination immunotherapy regimen may increase the potency and range of effectiveness of these MAbs in lymphoma patients.

Original languageEnglish (US)
Pages (from-to)944-956
Number of pages13
JournalLeukemia and Lymphoma
Volume48
Issue number5
DOIs
StatePublished - May 2007

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Keywords

  • CD20
  • HLA-DR
  • Immunotherapy
  • Lym-1
  • Lymphoma
  • Rituximab

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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