High-throughput technology and microfluidics can dramatically speed up therapeutic antibody discovery.
Cell culture for antibody production.
Therapeutic antibodies have become one of the fastest-growing drug classes used to treat cancer and autoimmune diseases. To find the most promising antibody, biotechnology and pharmaceutical companies usually need to produce large amounts of antibodies multiple times, to study a range of functional properties. This drawn-out process slows down drug research and development at every point.
Many companies are turning to contract research organizations, such as Biointron Biological Inc., that provide services for drug development, including the expression of a large number of antibodies in shorter periods.
Biointron runs a 4000m2 GMP-like lab facility.
Antibody production in two weeks
With its high-throughput platform, Biointron can produce antibodies from gene synthesis to antibody purification in as little as two weeks, sometimes even a week, depending on the scale.
“It’s very common to take five to six weeks to produce antibodies. If a company needs to produce four rounds of antibodies to find the most viable drug candidate, we can help them save two to three months of screening. This will dramatically accelerate their antibody drug development,” explains Changchun Zha, chief executive of Biointron.
The acceleration can be attributed to process reconstruction and capacity increase, says Zha. Biointron splits gene synthesis into several steps and runs some of the steps such as cloning and sequencing in parallel, so that it can be completed in three days, rather than two weeks via a conventional approach. Breakthroughs have also been achieved in other key technologies to increase the capacity, such as expression plasmid optimization. More genes can then be introduced into a target cell to improve the efficiency of antibody production.
An advanced shaker room enables production of more than 1,000 antibodies per batch.
Single B cell screening in a day
Traditionally, hybridoma technology — a five-step process based on the fusion of antigen-activated B cells with myeloma cells to create hybridomas, which are then screened to determine which produce the most suitable antibodies — is used to produce large numbers of monoclonal antibodies. This process can take as long as two months. With a single B cell screening platform, however, within a day Biointron can isolate single B cells, and find the ones secreting target antibody molecules.
The platform uses advanced droplet microfluidics, a technology that has emerged in the past few years. It was first used in diagnostics, but now has been applied to other fields, including antibody drug development. The single cells flow one by one in the droplets, while the testing and analysis of their functions can be completed at the same time to identify the desired single B cells.
“Integrated with single cell sequencing technology, the target antibody sequences can be easily obtained. This reduces the cycle of the whole process, from defining the target to generating preclinical samples, to around three months,” Zha says.
Biointron has a production area of over 14,600m2.
A promising future
Biointron is now supporting more than 1,000 companies from around the world. Looking ahead, Zha is certain that antibodies will be at the core of biomedical therapeutics.
In the next 20 years, therapeutic antibodies will have great potential, says Zha. Biointron has positioned itself as a common platform to serve various drug research companies to accelerate their antibody discovery. “That’s our one and only mission,” says Zha.