Current Advancements in Addressing Key Challenges of Therapeutic Antibody Design, Manufacture, and Formulation

Sifniotis, Vicki; Cruz, Esteban; Eroglu, Barbaros; Kayser, Veysel

doi:10.3390/antib8020036

Cited by 58 publications

(43 citation statements)

References 175 publications

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“…Some of the commonly used affinity tags are hexahistidine (His), glutathione S-transferase (GST), and maltose-binding protein (MBP) (Zhao et al, 2013). Protein A chromatography is the most widely used method for mAb purification (Gronemeyer et al, 2014;Sifniotis et al, 2019). The main problem associated with this chromatography is Protein A leachability, with non-specific binding of host cell protein, DNA, and other cell culture-derived impurities.…”

Section: Chromatography Processesmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

369

243

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Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

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Section: Chromatography Processesmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

369

243

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“…Several strategies, including nanoparticles, liposomes, and microencapsulation, have been developed to control mAb release and stability, prolonging their half-life. Moreover, these nanocarriers can increase tumor penetration of mAbs [ 115 ].…”

Section: Challenges Of Mabsmentioning

confidence: 99%

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

et al. 2021

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

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“…transportation networks, constant power supply), reliance on imports to source raw materials and equipment, lack of trained technical personnel, inadequate investments, issues with smuggling of substandard medicines from neighboring countries as well as unfavorable environmental or political conditions [ 59 ]. The production of mAbs continues to be a highly regulated and intensive process, with challenges such optimizing cellular productivity, ensuring a consistent glycosylation profile, effective purification during downstream processing and analytical technologies for rapid quality control and release [ 60 ].…”

Section: Supply Considerations and Modelsmentioning

confidence: 99%

Models to inform neutralizing antibody therapy strategies during pandemics: the case of SARS-CoV-2

Guttieres

Sinskey

Springs

2021

Antibody Therapeutics

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Background Neutralizing antibodies (nAbs) against SARS-CoV-2 can play an important role in reducing impacts of the COVID-19 pandemic, complementing ongoing public health efforts such as diagnostics and vaccination. Rapidly designing, manufacturing, and distributing nAbs requires significant planning across the product value chain and an understanding of the opportunities, challenges, and risks throughout. Methods A systems framework comprised of four critical components is presented to aid in developing effective end-to-end nAbs strategies in the context of a pandemic: 1) product design and optimization, 2) epidemiology, 3) demand, and 4) supply. Quantitative models are used to estimate product demand using available epidemiological data, simulate biomanufacturing operations from typical bioprocess parameters, and calculate antibody production costs to meet clinical needs under various realistic scenarios. Results In a US-based case study during the 9-month period from March 15 to December 15, 2020, the projected number of SARS-CoV-2 infections was 15.73 million. The estimated product volume needed to meet therapeutic demand for the maximum number of clinically eligible patients ranged between 6.3 tons and 31.5 tons for 0.5 g and 2.5 g dose sizes, respectively. The relative production scale and cost needed to meet demand are calculated for different centralized and distributed manufacturing scenarios. Conclusions Meeting demand for anti-SARS-CoV-2 nAbs requires significant manufacturing capacity and planning for appropriate administration in clinical settings. MIT Center for Biomedical Innovation’s data-driven tools presented can help inform time-critical decisions by providing insight into important operational and policy considerations for making nAbs broadly accessible, while considering time and resource constraints.

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Current Advancements in Addressing Key Challenges of Therapeutic Antibody Design, Manufacture, and Formulation

Cited by 58 publications

References 175 publications

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

Models to inform neutralizing antibody therapy strategies during pandemics: the case of SARS-CoV-2

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