title: Direct antilymphoma effects on human lymphoma cells of monotherapy and combination therapy with CD20 and HLA-DR antibodies and 90Y-labeled HLA-DR antibodies.
abstract: OBJECTIVE
  Monoclonal antibodies (mAb) in combination and mAbs combined with a radionuclide (radioimmunotherapy) have both been more effective in patients than mAb monotherapy.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, University of California Davis Health Sciences Center, Sacramento, California, USA. gldenardo@ucdavis.edu
authors.forename: Gerald L
authors.initials: GL
authors.lastname: DeNardo
authors.forename: Evan
authors.initials: E
authors.lastname: Tobin
authors.forename: Kaylund
authors.initials: K
authors.lastname: Chan
authors.forename: Bonnie M
authors.initials: BM
authors.lastname: Bradt
authors.forename: Sally J
authors.initials: SJ
authors.lastname: DeNardo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D018951:Antigens, CD20 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D003131:Combined Modality Therapy / Q000379:methods; D004306:Dose-Response Relationship, Immunologic; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008223:Lymphoma / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy; D051379:Mice; D008856:Microscopy, Fluorescence; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D014343:Trypan Blue / Q000494:pharmacology; D015021:Yttrium Radioisotopes / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D004396:Coloring Agents; D006684:HLA-DR Antigens; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D014343:Trypan Blue