Fastest antibody development

Fraunhofer ITEM researchers after preparation of monoclonal antibody doses. It was created using an innovative cell-pool method that significantly reduces the time to clinical trials. Credits: Fraunhofer ITEM / Holger Ziehr

Biopharmacy development is a long and costly process. It can take more than 10 years from the discovery of a new protein-based active ingredient to the release of a new drug. One of the major hurdles to this journey is the transition from labs to clinical trials. As a general rule, it takes 18 months to 2 years to manufacture this type of investigational drug for use in clinical trials. However, at the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, researchers in the pharmaceutical biotechnology department have developed a manufacturing method that shortens this step to just six months.

Around the world, research into therapeutics and vaccines to combat the coronavirus has increased dramatically in recent months. The pandemic once again emphasized how important it is to speed up the development and release of new drugs. But reality draws another picture. The development of suitable bioprocesses and the pilot production of protein-based drug candidates can take anything from 18 months to 2 years. Only then can clinical development begin. This is a complex process consisting of three phases. Many candidates are excluded during the first or second stage of a clinical trial because they are poorly tolerated or ineffective. Therefore, it is of utmost importance to obtain these clinical results as soon as possible. Researchers in Fraunhofer ITEM’s pharmaceutical biotechnology division have been able to significantly accelerate the process from discovering a new mechanism of action to preparing a new investigational drug ready for clinical trials. “Our new fast-track method reduces the time required for process development by months. Instead of 18 to 2 years, the entire development process, including pilot production, is completed in just 6 months.” Explains Professor Holger Ziehr. Fraunhofer ITEM’s Pharmaceutical Biotechnology Division in Braunschweig. This benefits the pharmaceutical industry and patients alike. In response to the COVID-19 pandemic, a new fast-track approach to bioprocess engineering was inevitably born. “We have worked closely with our industry partners to develop this new method,” says Ziehr. “This can reduce the time it takes to produce antibodies for clinical trials by one-third of the time normally required. Antibodies are proteins produced by immune cells. These proteins bind to pathogens. , Causes a mechanism that destroys pathogens. As a therapeutic agent, they support the immune system. “

Strategy development in consultation with Paul-Ehrlich-Institut

Synthesized antibodies reduce chronic inflammation and help treat neurodegenerative diseases and cancer. Therefore, researchers are optimistic that bioengineered antibodies can be used to treat COVID-19. “Anyone trying to develop a human antibody to treat SARS-CoV-2 is very keen on the fight against time,” explains Ziehr. “The period of 18 months to 2 years is simply too long, which is why we chose another production strategy, and suitable candidates for new active substances proceed to clinical research much faster. To solidify the strategy, this new approach was first submitted to Paul-Ehrlich-Institut, the German national vaccine approval body.

Like most other antibody production processes, the process developed at Fraunhofer ITEM is based on Chinese hamster ovary (CHO) cells. Approximately 80% of all bioengineered pharmaceutical grade proteins are produced with the help of this cell line. One of the main reasons for this is that the sugar chains that bind to the proteins newly synthesized in CHO cells are similar to those in humans.

Fastest antibody development

The new Fast Track process is being used to produce 3500 doses of monoclonal antibody. Credits: Fraunhofer ITEM / Holger Ziehr

Cell factory for antibody production

How did researchers develop new active ingredient candidates in such a short amount of time? In order to produce an antibody, it is necessary to introduce the genetic material of this antibody, that is, the DNA containing the corresponding antibody gene, into CHO cells. “We use so-called plasmids for this,” says Ziehr. “These are ring-shaped DNA molecules that are introduced into CHO cells by a process called transfection.” This transfection process takes place in a container containing a few milliliters of liquid nutrients and millions of cells. I will. The plasmid is then added to this culture, where it penetrates the cell and randomly integrates into the chromosome. The composition of liquid nutrients ensures that only cells that have integrated the antibody gene will proliferate. With the traditional approach, the tedious next step is to isolate and test individual cells until a CHO cell clone is identified that indicates optimal integration of the antibody gene in the genome.

This is a very time consuming process as a single cell division can take up to 48 hours. “This means that a year can easily pass before a usable clone becomes available, especially if the goal is to develop a drug for COVID-19. Too much. Therefore, we decided to skip the long process of cell segregation and work directly, which means that some cells accept the risk of taking up the genetic information from the antibody much better than others. However, the selection criteria applied to the cell pool were that most antibodies were also the ones that grew best. Some cells produced more antibodies and others were somewhat less. However, they all produced the same antibody.

New business model

The risk has paid off. The result is a stable cell pool that grows and produces large amounts of antibodies overall. In just six months, researchers were able to use this method to collect large amounts of drug-grade monoclonal antibodies and prepare 3500 doses for clinical trials. In addition, this fast track process can be used for almost all types of pharmaceutical grade proteins. As a result, Fraunhofer ITEM has created a whole new business model in the field of pharmaceutical biotechnology.

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Provided by Fraunhofer-Gesellschaft

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