title: Combination immunotherapy with anti-CD20 and anti-HLA-DR monoclonal antibodies induces synergistic anti-lymphoma effects in human lymphoma cell lines.
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(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). 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.
authors.affiliation: Department of Internal Medicine, University of California, Davis, CA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Tobin
authors.forename: Gerald
authors.initials: G
authors.lastname: Denardo
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Alan L
authors.initials: AL
authors.lastname: Epstein
authors.forename: Cathy
authors.initials: C
authors.lastname: Liu
authors.forename: Sally
authors.initials: S
authors.lastname: Denardo
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D003165:Complement System Proteins; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D006684:HLA-DR Antigens / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; D000069283:Rituximab; D003165:Complement System Proteins; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3