ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody-drug Conjugate.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Antibody-Based Therapeutics in Autoimmune Diseases: Mechanisms, Challenges, and Future Perspectives.International journal of molecular sciences · 2026Review
- Structural and Functional Insights into Viral and Fungal Proteins Involved in Chronic Inflammation and Their Biologic Treatments.Pharmaceutics · 2025Review
- PDE4 inhibitors in psoriasis therapy: current insights and future directions.Inflammopharmacology · 2025Review
- Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation.Nature communications · 2025Article
- The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Amlexanox Ameliorates Traumatic Brain Injury by Restoring Autophagy-Lysosomal Function via cAMP Signaling Modulation.International journal of biological sciences · 2025Article
- PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.Bioconjugate chemistry · 2023Review
- Natural Phosphodiesterase-4 Inhibitors with PotentialMolecules (Basel, Switzerland) · 2023Article
- A disruptive clickable antibody design for the generation of antibody-drug conjugates.Antibody therapeutics · 2023Article
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins.Molecules (Basel, Switzerland) · 2023Review
- Evaluation of an ester-linked immunosuppressive payload: A case study in understanding the stability and cleavability of ester-containing ADC linkers.Bioorganic & medicinal chemistry letters · 2022Article
- Nanoparticle Delivery of Novel PDE4B Inhibitor for the Treatment of Alcoholic Liver Disease.Pharmaceutics · 2022Article
- Making Sense of "Nonsense" and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications.International journal of molecular sciences · 2022Review
- Reprogramming natural proteins using unnatural amino acids.RSC advances · 2021Review
- Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases.Inflammatory bowel diseases · 2021Article
- Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond.Vaccines · 2021Review
- Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.International journal of molecular sciences · 2021Review
- Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase 4 (PDE4) inhibitors are approved for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects in the central nervous system and gastrointestinal tract, including nausea, emesis, headache, and diarrhea, have impeded the broader therapeutic application of PDE4 inhibitors. We sought to exploit the wealth of validation surrounding PDE4 inhibition by improving the therapeutic index through generation of an antibody-drug conjugate (ADC) that selectively targets immune cells through the CD11a antigen. The resulting ADC consisted of a human αCD11a antibody (based on efalizumab clone hu1124) conjugated to an analog of the highly potent PDE4 inhibitor GSK256066. Both the human αCD11a ADC and a mouse surrogate αCD11a ADC (based on the M17 clone) rapidly internalized into immune cells and suppressed lipololysaccharide (LPS)-induced TNFα secretion in primary human monocytes and mouse peritoneal cells, respectively. In a carrageenan-induced air pouch inflammation mouse model, treatment with the ADC significantly reduced inflammatory cytokine production in the air pouch exudate. Overall, these results provide compelling evidence for the feasibility of delivering drugs with anti-inflammatory activity selectively to the immune compartment via CD11a and the development of tissue-targeted PDE4 inhibitors as a promising therapeutic modality for treating inflammatory diseases.
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Registered trials
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