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Enhancing antimelanoma immune responses through apoptosis
Stacie R Bianco1, Juan Sun, Susan P Fosmire
1Center for Cancer Causation and Prevention, AMC Cancer Research Center and Donald Monk Cancer Research Foundation, Denver, Colorado 80214, USA.
Cancer Gene Therapy
|August 29, 2003
Summary
Priming immune cells with apoptotic melanoma cells enhances anti-tumor responses. Direct intratumoral Fas ligand (FasL) DNA delivery is safe and reduces tumor burden in dogs with melanoma.
Area of Science:
- Immunology
- Oncology
- Veterinary Medicine
Background:
- Melanoma often inactivates intrinsic apoptosis pathways.
- Tumor apoptosis can be leveraged to enhance anti-melanoma immune responses.
Purpose of the Study:
- To assess the feasibility of using tumor apoptosis to boost anti-melanoma immunity in canine melanoma.
- To investigate Fas ligand (FasL) for inducing extrinsic apoptosis in melanoma cells.
Main Methods:
- Priming peripheral blood mononuclear cells with apoptotic melanoma cells.
- Overexpressing FasL to induce extrinsic apoptosis.
- Intratumoral administration of FasL DNA in tumor-bearing dogs.
Main Results:
- Priming enhanced lymphokine-activated killing of tumor cells.
- FasL induced apoptosis in 5/6 melanoma cell lines expressing Fas mRNA.
- Intratumoral FasL DNA delivery was safe and reduced tumor burden in 3/5 dogs.
Conclusions:
- FasL overexpression effectively promotes apoptosis in Fas-positive melanomas.
- Priming immune cells with apoptotic tumor cells enhances anti-tumor responses.
- Intratumoral FasL DNA administration is a safe therapeutic gene delivery route.