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Direct Antilymphoma Effects on Human Lymphoma Cells of Monotherapy and Combination Therapy with CD20 and HLA-DR Antibodies and ⁹⁰Y-Labeled HLA-DR Antibodies

Authors' Affiliation: Departments of Internal Medicine and Radiology, University of California Davis Health Sciences Center, Sacramento, California

Requests for reprints: G.L. DeNardo, 1508 Alhambra Boulevard, #3100, Sacramento, CA 95816. Phone: 916-734-3787; Fax: 916-451-2857; E-mail: gldenardo{at}ucdavis.edu.

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. Assays of cell growth and death were done using microscopy and trypan blue dye.

Results: Lym-1 and rituximab, used singly, showed direct antilymphoma effects; those of Lym-1 were often more potent than those of rituximab. Combinations of these mAbs were more effective, sometimes synergistic, than either mAb singly, even in more resistant SU-DHL-4 cells. Conjugation of ⁹⁰Y to Lym-1 also augmented potency in all cell lines and overcame resistance to both Lym-1 and rituximab in Ramos cells.

Conclusions: Lym-1 exhibited substantially greater direct antilymphoma effects than rituximab in lymphoma cells in culture. Combination of Lym-1 with rituximab or ⁹⁰Y increased potency and overcame treatment resistance in lymphoma cells. Greater use of combination therapies of this type to increase potency and range of effectiveness seems likely to improve patient outcome.

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