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

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(1), combined with chLym-1(2), an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC(3) and CDC(4).

Direct antilymphoma effects on human lymphoma cells of monotherapy and combination therapy with CD20 and HLA-DR antibodies and 90Y-labeled HLA-DR antibodies.

Purpose: Monoclonal antibodies (mAb) in combination and mAbs combined with a radionuclide (radioimmunotherapy) have both been more effective in patients than mAb monotherapy.

Experimental Design: Using assays of cell growth and viability, the dose response and temporal characteristics of CD20 (rituximab) and HLA-DR (Lym-1) mAbs, singly and in combination, and of 90Y-conjugated Lym-1 mAb have been characterized in five human lymphoma cell lines (B35M, Raji, SU-DHL-4, SU-DHL-6, and Ramos) spanning Burkitt's to diffuse large cell lymphoma. Although Ramos had a lower HLA-DR density, these cell lines were otherwise selected because of high cell surface CD20 and HLA-DR abundance.

Antilymphoma effects of anti-HLA-DR and CD20 monoclonal antibodies (Lym-1 and Rituximab) on human lymphoma cells.

Aim: Anti-HLA-DR and anti-CD20 monoclonal antibodies (MAbs) have been effective for immunotherapy and radioimmunotherapy in non-Hodgkin's lymphoma (NHL). The aim of our study was to compare the antilymphoma effects of Lym-1 and rituximab in human lymphoma cell lines, using assays of viability, apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC), under conditions relevant to the clinic.

Methods: To characterize response relationships at varied concentrations of Lym-1 and rituximab, growth inhibition and cell death were assayed over 96 hours in four NHL cell lines derived from Burkitt's or large-cell lymphoma patients.