title: CD45 monoclonal antibody-mediated cytolysis of human NK and T lymphoma cells.
abstract: OBJECTIVE
  The CD45 rat monoclonal IgG2b antibodies YTH24.5 and YTH54.12 act synergistically to produce cytolysis of normal lymphocytes and have been safely given to patients in conditioning regimens for allogeneic stem cell transplantation. The antibodies are not lytic for hematopoietic stem cells, but the depletion of the lymphoid lineage cells is profound and sustained.
  
  
  METHODS
  We evaluated the YTH24.5 and YTH54.12 pair for complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and apoptotic and antiproliferative effects against a panel of non-Hodgkin's lymphoma (NHL) cell lines and against primary specimens.
  
  
  RESULTS
  Significant CDC activity was observed against two of two NK and one of four T lymphoma cell lines; moderate activity was seen against two of four T, and four of eight B lymphoma cell lines. In the responding cell lines, the lytic activity of YTH24.5 and YTH54.12 was as least as strong as that of alemtuzumab or antithymocyte globulin. The combination of YTH24.5 and YTH54.12 also induced ADCC in one of two NK and two of four T lymphoma cell lines, as well as three primary specimens, but was ineffective in B-NHL. The antibodies decreased viability in two of two NK and one lymphoma cell line, measurable as apoptosis or direct cell death in the cell lines NK92 and CEM, respectively. In a tumor model of Jurkat lymphoma in SCID mice, administration of YTH24.5 and YTH54.12 impaired local tumor growth and delayed systemic disease progression.
  
  
  CONCLUSIONS
  CD45 antibodies YTH24.5 and YTH54.12 have lytic activity against NK and T lymphoma cells via CDC and ADCC, are effective in a preclinical tumor model, and may be candidates for immunotherapeutic approaches to the treatment of human NK and T cell lymphoma.
authors.affiliation: Department of Hematology and Oncology, Georg-August-Universität Goettingen, Goettingen, Germany. gwulf@med.uni-goettingen.de
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Wulf
authors.forename: Anita
authors.initials: A
authors.lastname: Boehnke
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmerlein
authors.forename: Roland
authors.initials: R
authors.lastname: Schroers
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Lorenz
authors.initials: L
authors.lastname: Truemper
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017493:Leukocyte Common Antigens