APO-1 (CD95) mediated apoptosis in human T-ALL engrafted in SCID mice.
The monoclonal antibody anti-APO-1 induces apoptosis upon triggering the cell surface molecule APO-1 (CD95), a novel member of the tumor necrosis factor/nerve growth factor receptor superfamily. We tested the efficacy of APO-1 mediated apoptosis in a model system of human leukemia in SCID mice. T-ALL cells recovered from SCID mice were sensitive towards anti-APO-1 mediated apoptosis when tested in vitro. In vivo, treatment of leukemia-bearing SCID mice with anti-APO-1 induced programmed cell death in a substantial fraction of T-ALL cells, thus leading to significantly prolonged survival. Anti-APO-1 treatment, however, failed to completely eliminate all leukemic cells. This may be due to resistance towards anti-APO-1 mediated apoptosis in a fraction of T-ALL cells. Thus, identification of cellular programs which determine sensitivity and resistance towards apoptosis may provide new perspectives for rational therapeutic interventions.
Lücking-Famira
K M
KM
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center.
Daniel
P T
PT
Möller
P
P
Krammer
P H
PH
Debatin
K M
KM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology*; D017209:Apoptosis; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology* / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D019014:fas Receptor
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D019014:fas Receptor