Targeted Drug Delivery Using Immunoconjugates
| Autor: | Claudia Scotti, Rita Digilio, Luca Vecchia, Daniele Covini, Maria Valentina Pasquetto |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Immunoconjugates Immunology Protein Engineering Drug Delivery Systems Antigen Antigens Neoplasm Neoplasms Drug Discovery Animals Humans Immunology and Allergy Molecular Targeted Therapy Immunoglobulin Fragments Pharmacology Clinical Trials as Topic Protein Stability Drug discovery Chemistry Effector Prodrug Immunoconjugate Targeted drug delivery Liposomes Drug delivery PEGylation Cancer research Nanoparticles Immunotherapy |
| Zdroj: | Journal of Immunotherapy. 34:611-628 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/cji.0b013e318234ecf5 |
| Popis: | Antibody-drug conjugates (also known as "immunoconjugates") have only recently entered the arsenal of anticancer drugs, but the number of undergoing clinical trials including them is ever increasing and most therapeutic antibodies are now patented including their potential immunoconjugate derivatives. They typically consist of three components: antibody, linker, and cytotoxin. An antibody or antibody fragment targeted to a tumor-associated antigen acts as a carrier for drug delivery and can be conjugated by cleavable or uncleavable linkers to a variety of effector molecules, either a drug, toxin, radioisotope, enzyme (the latter also used in Antibody-Directed Enzyme Prodrug Therapy), or to drug-containing liposomes or nanoparticles. In this review, we propose a general outline of the field, starting from the diagnostic and clinical applications of this class of molecules. Special attention will be devoted to the principles and issues in molecular design (choice of tumor-associated antigen, critical milestones in antibody development, available alternatives for linkers and effector molecule, and strategies for fusion proteins building) to the importance of antibody affinity modulation to optimize therapeutic effect and the potential of emerging alternative scaffolds. Most of the power of these molecules is to reach high concentrations in the tumor, relatively unaffecting normal cells, although one drawback lies in their short half-life. In this respect, modifications of immunoconjugates, which have shown to strongly influence pharmacokinetics, like glycosylation and PEGylation, will be discussed. Undergoing clinical trials and active patents will be analyzed and problems present in clinical use will be reported. |
| Databáze: | OpenAIRE |
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