Awards

Christopher Love with Hadley Sikes of the Massachusetts Institute of Technology in the U.S. will develop a biomanufacturing platform for low-cost production of monoclonal antibodies based on a multidomain synthetic protein enabling both capture and purification of the antibody in a chromatography-free process. The synthetic protein will concentrate and recover antibodies in a single, mobile fluid phase, based on studies of the liquid-liquid phase transition of proteins into condensates that occur naturally in key cellular processes. They will design and test protein agents for affinity-based capture and condensation of monoclonal antibodies including the antimalarial MAM01, assess the co-expression of the synthetic protein and the target antibody product in a microbial expression system, and determine conditions for continuous recovery of the product. They will also create models of the technical and economic factors required for low-cost production from either microbial or mammalian cell expression systems.

This grant is one of three grants that are funded and administered by LifeArc.

The team at Isolere Bio, a Donaldson Life Sciences business in the U.S. will develop a biomanufacturing platform for low-cost production of monoclonal antibodies based on a multidomain synthetic protein enabling both capture and purification of the antibody in a chromatography-free process. The synthetic protein includes an antibody-binding affinity tag, and it enables liquid-liquid phase separation and selective concentration of the bound antibody. Key steps in the biomanufacturing process will be targeted to decrease costs and improve performance. This includes high-throughput experiments to identify conditions that improve the recycling of the synthetic protein, as well as tests to optimize the removal of viral contaminants during the purification process. Subsequently, larger-scale production will be piloted to identify the critical parameters required to scale up the platform.

Kelvin Lee of the University of Delaware in the U.S. will develop components of a biomanufacturing platform for low-cost production of monoclonal antibodies. The project will be implemented through the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) headquartered at the University of Delaware, with John Erickson of NIIMBL. It will focus on economic modeling, development of a mammalian cell line for expressing the antimalarial monoclonal antibody MAM01, and a head-to-head comparison of two antibody purification approaches, including isoelectric point purification (IPP) and continuous precipitation operations that reduce the number of process steps. Based on these tests, the platform components could be integrated into an end-to-end continuous processing system and co-developed with a next-generation facility design and regulatory strategy.

Antti Aalto with Pedro Gonçalves of VTT Technical Research Centre of Finland Ltd in Finland will develop a biomanufacturing platform for low-cost production of the antimalarial monoclonal antibody MAM01 using the filamentous fungus Trichoderma reesei as the protein expression system. They will create candidate production strains, incorporating different expression cassettes for synthetic MAM01 sequences and pairing them with different host strain genetic backgrounds optimized for expression. The resulting strains will be cultivated in small-scale bioreactors, testing multiple bioprocess conditions from cultivation through sequential steps for antibody capture and purification. They will create models of the technical and economic factors required for low-cost production, as well as an analysis of environmental impact, including water usage and waste generation of the production process, comparing this impact with available data for antibody production using mammalian cell culture systems.

This grant is one of three grants that are funded and administered by LifeArc.

Ashutosh Chilkoti of Duke University in the U.S. will develop a biomanufacturing platform for low-cost production of the antimalarial monoclonal antibody MAM01 based on a fusion protein enabling both capture and purification of the antibody in a chromatography-free process. The fusion protein will comprise an antibody-binding affinity tag fused to an elastin-like polypeptide (ELP) enabling liquid-liquid phase separation of the protein. It will be engineered to optimize its secretion by Chinese Hamster Ovary (CHO) cells and its reversible phase separation via its ELP domain. Protein co-expression strategies for antibody production will also be optimized, including comparing genomic integration of the fusion protein and MAM01 sequences in the same cell line versus in separate cell lines in the same bioreactor. These tests will be used to determine the purification strategy that maximizes MAM01 yield while minimizing process cost.

This grant is one of three grants that are funded and administered by LifeArc.

Anurag Rathore of the Indian Institute of Technology (IIT) Delhi with Abhishek Mathur of Enzene Biosciences Limited, both in India, will pilot test a continuous processing platform for monoclonal antibody biomanufacturing for its advantages compared to batch processing. The pilot will build on lessons from the platform operating at the Center of Excellence for Biopharmaceutical Technology at IIT, Delhi. It will demonstrate that the existing biomanufacturing platform in an academic setting can be scaled up in a commercial setting. It will validate the decreased cost of goods and increased production relative to batch manufacturing, and it will provide technical and economic data, with details on integrating operations from cell culture through final formulation into a seamless, automated process. This data will guide efforts to increase access and affordability of monoclonal antibody products by manufacturing them in low- and middle-income settings.

James Brown of Bondi Bio Pty Ltd with Jake Baum at UNSW Sydney, both in Australia, will develop a biomanufacturing platform for low-cost production of the antimalarial monoclonal antibody MAM01 using the photosynthetic cyanobacterium Synechococcus as the protein expression system. They will engineer a cyanobacterial strain to express MAM01, grow it in high-density batch cultivation, optimize cell lysis and clarification to ensure maximum product yield and integrity, and purify fully assembled MAM01 by standard column chromatography. Purified MAM01 will be analyzed to confirm it has the correct mass, folding, and assembly, including complete disulfide bond formation and the expected glycosylation, and the strain will be engineered further where required. They will also use these experimental results to outline a facility design and an economic model for MAM01 biomanufacturing, focusing on the initial process steps of batch cultivation, centrifugation, and cell lysis.

Michael Betenbaugh with Honggang Cui of Johns Hopkins University in the U.S. will develop a biomanufacturing platform for low-cost production of the antimalarial monoclonal antibody MAM01, combining a fungal expression system with a nanofiber-bound peptide technology for antibody capture and purification. Collaborating with Dyadic International and with Thermo Fisher Scientific, they will optimize the fermentation media and bioprocess conditions in the expression system, which uses the thermophilic filamentous fungus Thermothelomyces heterothallica C1. They will also optimize conditions for the selective capture, separation, and recovery of the antibody along with recycling of the antibody-binding peptide. They will integrate these conditions, assess and further optimize them to reduce production costs, and demonstrate the scalability of the platform.

Cristiana Boi with Ruben Carbonell of North Carolina State University in the U.S. will develop a purification system for the antimalarial monoclonal antibody MAM01 that uses an all-membrane chromatography process with single-use membranes made from low-cost nonwoven materials. This system will be combined with a protein expression system using the thermophilic filamentous fungus Thermothelomyces heterothallica C1 to create a low-cost biomanufacturing platform. Collaborating with Dyadic International, they will obtain MAM01-containing supernatants from the expression system and analyze its components to guide development of the purification system. Based on these results, small-scale purification experiments will be performed, testing suitable membrane-coupled ligands, membrane configurations, purification conditions and steps, and integration of the system into single-use cassettes. They will also determine the process requirements to scale up the platform.

Vijayalakshmi Ramshankar of the Cancer Institute (WIA) in India will perform a study of air pollution's effects on lung cancer in India. To focus on the links specifically with air pollution they will recruit non-smoking lung cancer patients in the city of Chennai. They will screen these patients for EGFR driver mutations, known to promote air pollution-related lung cancer, and measure the cytokine and miRNA profiles in their blood through periodic sampling. They will also perform this blood analysis in patients' asymptomatic household family members, who will be offered further testing (low-dose spiral CT scanning) for early cancer detection. Air pollution will be assessed in these households using a device for continuously monitoring indoor exposure. They will perform statistical analysis combining the biological and environmental data to better understand how air pollution affects lung cancer risk and to identify a high-risk signature to guide early screening.