[Viral transfer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gene therapy]

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cancer cell death via the extrinsic apoptosis pathway.
• Gene therapy using TRAIL has shown preclinical success in various cancers, including prostate, breast, and lung cancer.
• TRAIL gene therapy offers a potential alternative to chemotherapy with fewer side effects.

Purpose of the Study:

• To evaluate the efficacy and safety of TRAIL gene therapy in preclinical and early clinical settings.
• To explore the potential of adenoviral vectors (AdV) encoding TRAIL as an anti-tumor therapeutic.
• To assess TRAIL's application in other diseases like rheumatoid arthritis and type 1 diabetes.

Main Methods:

• Viral transfer of the TRAIL transgene into various cancer cell lines (in vitro).
• Administration of AdV encoding TRAIL in preclinical cancer models.
• Conducting a Phase I clinical trial for prostate cancer patients.

Main Results:

• Preclinical studies demonstrated significant apoptosis of target cancer cells and disease regression.
• TRAIL gene therapy showed no adverse effects in preclinical models, unlike chemotherapy.
• The Phase I trial indicated local inflammation and apoptosis in prostate cancer patients receiving AdV-TRAIL.

Conclusions:

• TRAIL gene therapy, particularly using AdV, holds significant potential for anti-tumor applications.
• Further clinical investigation is warranted to optimize AdV-TRAIL delivery and assess safety and efficacy.
• TRAIL-based therapies may also have applications beyond oncology, such as in autoimmune diseases.