title: Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin's lymphoma.
abstract: The monoclonal antibody against CD20, rituximab, alone, or as part of combination therapies, is standard therapy for non-Hodgkin's B-cell lymphoma. Despite significantly better clinical results obtained for beta-emitting radioimmunoconjugates (RICs), RICs targeting CD20 are not commonly used in medical practice, partly because of competition for the CD20 target. Therefore, novel therapeutic approaches against other antigens are intriguing. Here, the binding properties of a novel antibody against CD37 (tetulomab) were compared with those of rituximab. The therapeutic effect of (177)Lu-tetulomab was compared with (177)Lu-rituximab on Daudi cells in vitro. The biodistribution, therapeutic and toxic effects of (177)Lu-tetulomab and unlabeled tetulomab were determined in SCID mice injected with Daudi cells. The affinity of tetulomab to CD37 was similar to the affinity of rituximab to CD20, but the CD37-tetulomab complex was internalized 10-times faster than the CD20-rituximab complex. At the same concentration of antibody, (177)Lu-tetulomab was significantly more efficient in inhibiting cell growth than was (177)Lu-rituximab, even though the cell-bound activity of (177)Lu-rituximab was higher. Treatment with 50 and 100 MBq/kg (177)Lu-tetulomab resulted in significantly increased survival of mice, compared with control groups treated with tetulomab or saline. The CD37 epitope recognized by tetulomab was highly expressed in 216 out of 217 tumor biopsies from patients with B-cell lymphoma. This work warrants further pre-clinical and clinical studies of (177)Lu-tetulomab.
authors.affiliation: Nordic Nanovector AS, Kjelsåsveien 168 B, 0884 Oslo, Norway. jd@nordicnanovector.no
authors.forename: Jostein
authors.initials: J
authors.lastname: Dahle
authors.forename: Ada H V
authors.initials: AH
authors.lastname: Repetto-Llamazares
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Mollatt
authors.forename: Katrine B
authors.initials: KB
authors.lastname: Melhus
authors.forename: Oyvind S
authors.initials: OS
authors.lastname: Bruland
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.forename: Roy H
authors.initials: RH
authors.lastname: Larsen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage; D007167:Immunotherapy; D008187:Lutetium / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D011868:Radioisotopes / Q000008:administration & dosage; D000069283:Rituximab; D059470:Tetraspanins / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C059071:CD37 protein, human; D018796:Immunoconjugates; D011868:Radioisotopes; D059470:Tetraspanins; D000069283:Rituximab; D008187:Lutetium; C581327:tetulomab tetraxetan lu-177