Monoclonal antibody-mediated tumor regression by induction of apoptosis.
To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.
Trauth
B C
BC
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Klas
C
C
Peters
A M
AM
Matzku
S
S
Möller
P
P
Falk
W
W
Debatin
K M
KM
Krammer
P H
PH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D001345:Autoradiography; D001402:B-Lymphocytes / Q000276:immunology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000628:therapy; D002470:Cell Survival; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D011233:Precipitin Tests; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm