Abstract
Antibodies (Abs), often associated with antimicrobial and antitumor agents, have emerged as an important class of novel drugs for antigen-driven therapeutic purposes in diverse clinical settings, including oncology and infectious diseases. Abs commonly give rise in the treated host to anti-Ab responses, which may induce adverse reactions and limit their therapeutic efficacy. Their modular domain architecture has been exploited to generate alternative reduced formats (Fabs, scFvs, dAbs, minibodies, multibodies), essentially devoid of the Fc region. The presence of complementarity determining regions (CDRs) ensures the maintenance of selective binding to antigens and supports their use for biotechnological and therapeutic applications. Paradigmatic Abs mimicking the wide-spectrum antimicrobial activity of a yeast killer toxin (killer Abs) have revealed the existence of a family of Abs exerting a direct in vitro and/or in vivo microbicidal activity. Based on the variable sequence of an antiidiotypic recombinant killer Ab, CDR-related peptides have been synthesized, engineered by alanine-scanning and selected according to antimicrobial, antiviral and immunomodulatory properties. Irrespective of the native Ab specificity, synthetic CDRs from unrelated murine and human monoclonal Abs, have shown to display differential in vitro, in vivo and/or ex vivo antifungal (Candida albicans), antiviral (HIV-1) and antitumor (melanoma cells) activities. Alanine substitution of single residues of synthetic CDR peptides resulted in further differential increased/unaltered/decreased biological activity. The intriguing potential of Abs as source of antiinfective and antitumor therapeutics will be discussed, in light of recent advances in peptide design, stability and delivery.
Keywords: Antibodies, therapeutic antibodies, microbicidal antibodies, synthetic CDRs, killer peptides, antiinfective peptides, antitumor peptides
Current Medicinal Chemistry
Title: Antibodies as Crypts of Antiinfective and Antitumor Peptides
Volume: 16 Issue: 18
Author(s): W. Magliani, S. Conti, R. L.O.R. Cunha, L. R. Travassos and L. Polonelli
Affiliation:
Keywords: Antibodies, therapeutic antibodies, microbicidal antibodies, synthetic CDRs, killer peptides, antiinfective peptides, antitumor peptides
Abstract: Antibodies (Abs), often associated with antimicrobial and antitumor agents, have emerged as an important class of novel drugs for antigen-driven therapeutic purposes in diverse clinical settings, including oncology and infectious diseases. Abs commonly give rise in the treated host to anti-Ab responses, which may induce adverse reactions and limit their therapeutic efficacy. Their modular domain architecture has been exploited to generate alternative reduced formats (Fabs, scFvs, dAbs, minibodies, multibodies), essentially devoid of the Fc region. The presence of complementarity determining regions (CDRs) ensures the maintenance of selective binding to antigens and supports their use for biotechnological and therapeutic applications. Paradigmatic Abs mimicking the wide-spectrum antimicrobial activity of a yeast killer toxin (killer Abs) have revealed the existence of a family of Abs exerting a direct in vitro and/or in vivo microbicidal activity. Based on the variable sequence of an antiidiotypic recombinant killer Ab, CDR-related peptides have been synthesized, engineered by alanine-scanning and selected according to antimicrobial, antiviral and immunomodulatory properties. Irrespective of the native Ab specificity, synthetic CDRs from unrelated murine and human monoclonal Abs, have shown to display differential in vitro, in vivo and/or ex vivo antifungal (Candida albicans), antiviral (HIV-1) and antitumor (melanoma cells) activities. Alanine substitution of single residues of synthetic CDR peptides resulted in further differential increased/unaltered/decreased biological activity. The intriguing potential of Abs as source of antiinfective and antitumor therapeutics will be discussed, in light of recent advances in peptide design, stability and delivery.
Export Options
About this article
Cite this article as:
Magliani W., Conti S., Cunha L.O.R. R., Travassos R. L. and Polonelli L., Antibodies as Crypts of Antiinfective and Antitumor Peptides, Current Medicinal Chemistry 2009; 16 (18) . https://dx.doi.org/10.2174/092986709788453104
DOI https://dx.doi.org/10.2174/092986709788453104 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents
Current Medicinal Chemistry Intracellular Drug Delivery: Mechanisms for Cell Entry
Current Pharmaceutical Design Transient Receptor Potential Channels, the Kidney and Hypertension
Current Hypertension Reviews Natural Compounds with Cell Growth Inhibitory Activity in Human Tumor Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Gene Expression Abnormalities in Thymoma
Current Pharmacogenomics Novel Aglycones of Steroidal Glycoalkaloids as Potent Tyrosine Kinase Inhibitors: Role in VEGF and EGF Receptors Targeted Angiogenesis
Letters in Drug Design & Discovery α7 Nicotinic Acetylcholine Receptor Subunit in Angiogenesis and Epithelial to Mesenchymal Transition
Current Drug Targets Novel Marine and Microbial Natural Product Inhibitors of Vacuolar ATPase
Current Medicinal Chemistry Potential Crossreactivity of Human Immune Responses Against HCMV Glycoprotein B
Current Drug Discovery Technologies p75NTR as a Therapeutic Target for Neuropsychiatric Diseases
Current Molecular Pharmacology Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment
Current Drug Targets Familial Colorectal Cancer Type X
Current Genomics Effects of LPA and S1P on the Nervous System and Implications for Their Involvement in Disease
Current Drug Targets Recent Advances in Targeted Anti-Vasculature Therapy: The Neuroblastoma Model
Current Drug Targets Design, Synthesis and Antitumor Activities of Bis-arylureas and Bis-arylamides Based on1H-benzo[d]imidazole Moiety as Novel BRaf<sup>V600E</sup>/VEGFR2 Dual inhibitors
Letters in Drug Design & Discovery Recent Advances in Ethnopharmacological and Toxicological Properties of Bioactive Compounds from <i>Aloe barbadensis</i> (Miller), <i>Aloe vera</i>
Current Bioactive Compounds Acrylamide Induced Toxicity and the Propensity of Phytochemicals in Amelioration: A Review
Central Nervous System Agents in Medicinal Chemistry Progress in the Development of Bestatin Analogues as Aminopeptidases Inhibitors
Current Medicinal Chemistry NRF2-Dependent Glutamate-L-Cysteine Ligase Catalytic Subunit Expression Mediates Insulin Protection Against Hyperglycemia-Induced Brain Endothelial Cell Apoptosis
Current Neurovascular Research Drug Synergy Prediction Using Dynamic Mutation Based Differential Evolution
Current Pharmaceutical Design