CD45 monoclonal antibody-mediated cytolysis of human NK and T lymphoma cells.
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.
Wulf
Gerald G
GG
Department of Hematology and Oncology, Georg-August-Universität Goettingen, Goettingen, Germany. gwulf@med.uni-goettingen.de
Boehnke
Anita
A
Chapuy
Bjoern
B
Glass
Bertram
B
Hemmerlein
Bernhard
B
Schroers
Roland
R
Brenner
Malcolm K
MK
Truemper
Lorenz
L
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
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017493:Leukocyte Common Antigens