Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics
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The anti-CD20 antibody rituximab (RTX; Rituxan®, MabThera®) was the first anti-cancer antibody approved by the US Food and Drug Administration in 1997 and it is now the most-studied unconjugated therapeutic antibody. The knowledge gained over the past 15 y on the pharmacodynamics (PD) of this antibody has led to the development of a new generation of anti-CD20 antibodies with enhanced efficacy in vitro. Studies on the pharmacokinetics (PK) properties and the effect of factors such as tumor load and localization, antibody concentration in the circulation and gender on both PK and clinical response has allowed the design of optimized schedules and novel routes of RTX administration. Although clinical results using newer anti-CD20 antibodies, such as ofatumumab and obinutuzumab, and novel administration schedules for RTX are still being evaluated, the knowledge gained so far on RTX PK and PD should also be relevant for other unconjugated monoclonal antibody therapeutics, and will be critically reviewed here.
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Fc-mediated effector functions upon antibody-antigen interaction may contribute to observed clearance by depleting target cells, as shown for rituximab.
“For example, Fc‐mediated effector functions (ADCC or CDC) upon antibody–antigen interaction may contribute to observed clearance by depleting target cells, as shown for rituximab.34”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [34]
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- Authors
- Golay, J., Semenzato, G., Rambaldi, A., Foà, R., Gaidano, G., Gamba, E., Pane, F., Pinto, A., Specchia, G., Zaja, F., & Regazzi, M.
- Affiliations
- Ospedale Papa Giovanni XXIII (IT)
- University of Padua (IT)
- Sapienza University of Rome (IT)
- Roche (Italy) (IT)
- CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- University of Bari Aldo Moro (IT)
- Ospedale Santa Maria della Misericordia di Udine (IT)
- Policlinico San Matteo Fondazione (IT)
- Corresponding author
- Golay, Josée
- ORCID
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2013-11
- Volume
- 5
- Issue
- 6
- Pages
- 826-837
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- PMC
- PMC3896596
- OpenAlex
- W2016955385
- Cited by
- 148
- References
- 107
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 13 · 2022: 9 · 2021: 19 · 2020: 8 · 2019: 16 · 2018: 10 · 2017: 15 · 2016: 9 · 2015: 11 · 2014: 3
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- mAbs (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- rituximab, pharmacokinetics, pharmacodynamics, anti-CD20 monoclonal antibody, therapeutic monoclonal antibodies, ofatumumab, obinutuzumab, dosing regimen, route of administration, tumor burden, gender effects, clinical response
- MeSH terms
- Rituximab, Antineoplastic Agents, Humans, Models, Biological, Neoplasms, Protein Binding, Sex Factors, Antibodies, Monoclonal, Murine-Derived
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