Protein aggregation and immunogenicity of biotherapeutics.

International Journal of Pharmaceutics
Ngoc B Pham, Wilson S Meng

Abstract

Recombinant proteins are the mainstay of biopharmaceuticals. A key challenge in the manufacturing and formulation of protein biologic products is the tendency for the active pharmaceutical ingredients to aggregate, resulting in irreversible drug loss, and an increase in immunogenicity risk. While the molecular mechanisms of protein aggregation have been discussed extensively in the literature, knowledge gaps remain in connecting the phenomenon in the context of immunogenicity of biotherapeutics. In this review, we discussed factors that drive aggregation of pharmaceutical recombinant proteins, and highlighted methods of prediction and mitigation that can be deployed through the development stages, from formulation to bioproduction. The purpose is to stimulate new dialogs that would bridge the interface between physical characterizations of protein aggregates in biotherapeutics and the functional attributes of the immune system.

References

Aug 20, 1992·Journal of Molecular Biology·D F StickleG D Rose
Aug 7, 1990·Biochemistry·K A Dill
Jul 20, 1973·Science·C B Anfinsen
Jul 20, 1993·Journal of Molecular Biology·P L Privalov, G I Makhatadze
Jan 1, 1996·Methods in Enzymology·S L Wu, B L Karger
Sep 2, 1998·Current Opinion in Immunology·E Szomolanyi-Tsuda, R M Welsh
Oct 28, 1998·Biophysical Journal·B L NealA M Lenhoff
Aug 18, 2001·Biophysical Journal·A NeaguA Dér
Feb 1, 2002·Biochemical and Biophysical Research Communications·F EdwinM V Jagannadham
Apr 25, 2003·Analytical Biochemistry·Sarah E Bondos, Alicia Bicknell
Oct 27, 2004·Biophysical Chemistry·Susanne MoelbertPaolo De Los Rios
May 29, 2008·Multiple Sclerosis : Clinical and Laboratory Research·P S SorensenK Bendtzen
Jun 13, 2009·Current Pharmaceutical Biotechnology·John S Philo, Tsutomu Arakawa
Jan 9, 2010·Annual Review of Physical Chemistry·Yanjie Zhang, Paul S Cremer
Mar 24, 2010·Journal of Pharmaceutical Sciences·Satish K SinghThomas Spitznagel
Aug 17, 2010·Biomaterials·Jai S RudraJoel H Collier
Sep 21, 2010·The Journal of Physical Chemistry. B·Thomas M SchererAllen P Minton
Apr 14, 2011·JAMA : the Journal of the American Medical Association·Geertje M BarteldsGerrit Jan Wolbink
Oct 13, 2011·Journal of Pharmaceutical Sciences·Linda O NarhiDeepak Sharma
May 23, 2014·Nucleic Acids Research·Ian WalshAntonio Trovato
Jun 9, 2014·Trends in Biotechnology·Christopher J Roberts
Jul 23, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Puthusserickal A HassanGunjan Verma
Sep 1, 2014·Current Opinion in Biotechnology·Christopher J Roberts
Dec 17, 2014·Biological & Pharmaceutical Bulletin·Yoichi IshiiKaori Wakamatsu
Jan 30, 2015·Pharmaceutical Research·Juliana BessaAntonio Iglesias
Mar 5, 2015·Journal of Pharmaceutical Sciences·Maliheh ShomaliTheodore W Randolph
Apr 18, 2015·The Journal of Physical Chemistry. B·Gregory V BarnettChristopher J Roberts
Aug 12, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·A Quigley, D R Williams

❮ Previous
Next ❯

Citations

Feb 21, 2021·BMC Immunology·Lobna Abdel Aziz KilanyHamdallah Hafez Zedan
Apr 30, 2021·Frontiers in Chemistry·Chaitra ChandrashekarJohn D Wade
Aug 13, 2021·Pharmaceutical Research·Shrenik MehtaAlavattam Sreedhara

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.