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APO-1 (CD95) mediated apoptosis in human T-ALL engrafted in SCID mice
K M Lücking-Famira1, P T Daniel, P Möller
1Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center.
Abstract:
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.
Insights
The monoclonal antibody anti-APO-1 triggers apoptosis in human leukemia cells, prolonging survival in mice. Further research is needed to overcome resistance to this apoptosis-inducing therapy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- The APO-1 (CD95) molecule is a cell surface receptor involved in programmed cell death.
- Monoclonal antibodies targeting APO-1 can induce apoptosis, a key mechanism in cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of anti-APO-1 antibody in a SCID mouse model of human T-cell acute lymphoblastic leukemia (T-ALL).
- To investigate the potential of APO-1 mediated apoptosis as a therapeutic strategy for T-ALL.
Main Methods:
- Human T-ALL cells were xenografted into SCID mice.
- Leukemia-bearing mice were treated with the anti-APO-1 monoclonal antibody.
- In vitro and in vivo apoptosis assays were performed on T-ALL cells.
Main Results:
- Anti-APO-1 treatment induced apoptosis in a significant fraction of T-ALL cells in vivo.
- Treatment led to significantly prolonged survival of leukemia-bearing SCID mice.
- Complete elimination of leukemic cells was not achieved, suggesting resistance mechanisms.
Conclusions:
- APO-1 mediated apoptosis shows therapeutic potential against human T-ALL in vivo.
- Resistance to anti-APO-1 therapy exists in a subset of T-ALL cells.
- Understanding apoptosis sensitivity and resistance is crucial for developing effective T-ALL treatments.