Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 1, monoclonal antibodies, antibody-drug conjugates and bispecific T-cell engagers
| Autor: | Angelo Paci, Julia Delahousse, Sophie Broutin, Aude Desnoyer, Christophe Maritaz, Olivier Mir, Nathalie Chaput, Louis Blondel |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Drug Cancer Research medicine.medical_specialty Immunoconjugates medicine.drug_class Metabolic Clearance Rate T cell media_common.quotation_subject T-Lymphocytes Monoclonal antibody Drug Administration Schedule 03 medical and health sciences 0302 clinical medicine Antineoplastic Agents Immunological Pharmacokinetics Internal medicine Neoplasms Antibodies Bispecific medicine Humans media_common medicine.diagnostic_test biology Dose-Response Relationship Drug business.industry Antibodies Monoclonal 030104 developmental biology medicine.anatomical_structure Therapeutic drug monitoring 030220 oncology & carcinogenesis Pharmacodynamics biology.protein Rituximab Antibody Drug Monitoring business medicine.drug Half-Life |
| Zdroj: | European journal of cancer (Oxford, England : 1990). 128 |
| ISSN: | 1879-0852 |
| Popis: | More than 25 therapeutic monoclonal antibodies (mAbs) used in oncology have been approved since 1997. Their nature has been largely modified through the last 20 years, from the chimeric IgG1 rituximab with pharmacokinetic parameters specific of murin or chimeric mAbs to humanized or human mAbs. Doses and administration frequency have been chosen based on this nature. More recently, the developed and registered mAbs are mostly IgG1, IgG2, IgG3 or IgG4 humanized or 100% human. Therefore, their behavior is different from the first mAbs authorized leading to lower systemic clearance and shorter half-life due to higher cellular uptake balanced by FcRn recognition with recirculation. The complexity of the pharmacokinetics and the pharmacokinetics/pharmacodynamics relation are increased for antibody-drug conjugates or bispecific T-cell engagers. However, significant number of studies reported pharmacokinetics/pharmacodynamics relations, with positive exposure-response link justifying the exploration of the pharmacokinetics in routine clinical practice of these therapeutic mAbs to prevent treatment failures and to limit their toxicities. |
| Databáze: | OpenAIRE |
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