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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy
Agathe Dubuisson1,2,3, Olivier Micheau4,5,6
1University Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21079 Dijon, France. Agathe.Dubuisson@u-bourgogne.fr.
Abstract:
Developing therapeutics that induce apoptosis in cancer cells has become an increasingly attractive approach for the past 30 years. The discovery of tumor necrosis factor (TNF) superfamily members and more specifically TNF-related apoptosis-inducing ligand (TRAIL), the only cytokine of the family capable of eradicating selectively cancer cells, led to the development of numerous TRAIL derivatives targeting death receptor 4 (DR4) and death receptor 5 (DR5) for cancer therapy. With a few exceptions, preliminary attempts to use recombinant TRAIL, agonistic antibodies, or derivatives to target TRAIL agonist receptors in the clinic have been fairly disappointing. Nonetheless, a tremendous effort, worldwide, is being put into the development of novel strategic options to target TRAIL receptors. Antibodies and derivatives allow for the design of novel and efficient agonists. We summarize and discuss here the advantages and drawbacks of the soar of TRAIL therapeutics, from the first developments to the next generation of agonistic products, with a particular insight on new concepts.
Insights
Targeting cancer cells via apoptosis is a key strategy. While early TRAIL-based therapies showed limited success, new antibody designs offer improved cancer treatment options.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Apoptosis induction in cancer cells is a significant therapeutic strategy.
- Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) selectively targets cancer cells.
- TRAIL derivatives targeting death receptors (DR4/DR5) have been explored for cancer therapy.
Purpose of the Study:
- To review the evolution of TRAIL therapeutics.
- To discuss the advantages and disadvantages of TRAIL-based cancer treatments.
- To provide insight into next-generation TRAIL agonist development.
Main Methods:
- Literature review of TRAIL therapeutics.
- Analysis of clinical trial outcomes for TRAIL derivatives.
- Discussion of novel antibody and derivative designs targeting TRAIL receptors.
Main Results:
- Initial clinical applications of recombinant TRAIL and derivatives yielded disappointing results.
- Significant global efforts are ongoing to develop improved TRAIL receptor-targeting strategies.
- Novel antibodies and derivatives show promise for enhanced agonist design.
Conclusions:
- Despite early setbacks, TRAIL receptor-targeted therapies remain a promising area in oncology.
- Next-generation agonists, particularly antibody-based, are crucial for overcoming previous limitations.
- Continued research into novel TRAIL therapeutic concepts is essential for effective cancer treatment.
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