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A trial to kill tumor cells through Fas (CD95)-mediated apoptosis in vivo
M Shimizu1, T Yoshimoto, S Nagata
1Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Abstract:
We tried to induce tumor cell death in vivo through Fas (CD95)-mediated apoptosis. Murine hepatoma MH 134 (Fas-) was transfected with murine Fas antigen cDNA. Fas+ F6b but not Fas- N1d cells underwent apoptosis after treatment with anti-Fas antibody in vitro. The possibility of eradicating tumor cells in vivo with anti-Fas antibody was investigated using double-mutant gld/gld lpr/lpr mice which lack both Fas ligand (FasL) and Fas to avoid cytotoxic activity of the antibody to the liver and interference from endogenous FasL. A single administration of anti-Fas antibody efficiently suppressed the growth of F6b tumors but not that of N1d tumors in these mice. Thus, the therapy with Fas-FasL system may be a promising approach for cancer treatment, and this model is useful for study on in vivo apoptosis-mediated antitumor activity.
Insights
This study explored using the Fas-Fas ligand system to induce tumor cell death. Researchers found that anti-Fas antibody treatment effectively suppressed tumor growth in vivo, suggesting a promising cancer therapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The Fas (CD95) receptor and its ligand (FasL) pathway are critical for inducing apoptosis (programmed cell death).
- Targeting this pathway offers a potential strategy for cancer treatment by eliminating tumor cells.
Purpose of the Study:
- To investigate the efficacy of inducing tumor cell death in vivo using the Fas-mediated apoptosis pathway.
- To evaluate the potential of anti-Fas antibody therapy for cancer treatment.
Main Methods:
- Murine hepatoma cells (MH 134) were transfected to express Fas antigen, creating Fas+ (F6b) and Fas- (N1d) cell lines.
- In vitro studies assessed apoptosis induction by anti-Fas antibody.
- In vivo experiments utilized double-mutant gld/gld lpr/lpr mice (lacking FasL and Fas) to test anti-Fas antibody efficacy on tumor growth.
Main Results:
- Fas+ F6b cells underwent apoptosis upon anti-Fas antibody treatment in vitro, while Fas- N1d cells did not.
- A single administration of anti-Fas antibody significantly suppressed F6b tumor growth in vivo.
- N1d tumor growth was not affected by the anti-Fas antibody treatment in vivo.
Conclusions:
- The Fas-Fas ligand system holds promise as a therapeutic approach for cancer treatment.
- The developed mouse model is valuable for studying in vivo apoptosis-mediated antitumor activity.