Three University of Missouri graduates create biochemical business to find new cancer drugs

When a person receives a cancer diagnosis, treatment can often include chemotherapy. This method of treating cancer also can affect healthy cells.

But what if there was a drug on the market that, instead of affecting an entire person's body, could impact only the cancerous cells?

That is what three University of Missouri graduates have set out to do with their company, Cell Origins.

By using a method of drug discovery developed by Nobel Laureate George Smith, MU professor emeritus, known as phage display, Chief Operations Officer Jessica Newton-Northup, Chief Scientific Officer Mette Soendergaard and CEO Leann Kuhlmann-Qi, are working with other labs or pharmaceutical companies who may need access to a phage library or need to create a custom library to discover new drugs, not necessarily only for cancer treatments, but a variety of diseases.

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"What makes us unique is having three Mizzou alumnas. Our home (to us) is Mizzou in Columbia," Soendergaard said.

This work is what Cell Origins can do with its phage libraries, and it is developing a standardized testing kit for use in other labs. The main focus of Cell Origins is on development of cancer drug treatments, though, Soendergaard said.

While Newton-Northup and Soendergaard studied Smith's phage display, their research was using that for cancer treatments in the lab operated by Susan Deutscher, professor of biochemistry at MU's College of Agriculture, Food and Natural Resources.

The idea for Cell Origins came before Smith was awarded the Nobel Prize in 2018, but officially got its start in 2019 when Newton-Northup and Soendergaard connected with Kuhlmann-Qi to aid the business development.

"We started out as (lab) co-workers who quickly became really good friends. She is the godmother of my oldest child," Soendergaard said about Newton-Northup, where after graduation Newton-Northup already "was working with another startup out of the business incubator. In there, she was working with (Kuhlmann-Qi, who) is a MBA and her thing is working with startups."

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The trio received startup capital via a National Institutes of Health Small Business Innovation Research grant for Cell Origins once they started working together. Soendergaard was at MU between 2009 and 2014 to receive her Ph.D., under mentorship from Deutscher.

Cell Origins continues to operate from the MU campus out of the Life Science Incubator at the Missouri Innovation Center. Newton-Northup handles the day-to-day operations, while Soendergaard and Kuhlmann-Qi work remotely.

What a phage library is; how it helps discover new drugs

What exactly is a phage? While a person may have heard the term phage in science fiction, such as from "Star Trek," phages are very real.

To put it simply, it is a virus that attacks and can kill bacteria. The full name is bacteriophage.

A phage library can be billions or tens of billions of "books" of phage viruses, each with millions or billions of copies within each book in the library. Each phage book has a slightly different grouping of amino acids, known as a peptide or an antibody, attached to the phage that does not interfere with its ability to attack bacteria, most often a harmless e. coli strain of bacteria.

The reason phages are used for drug discovery is because of their ability to replicate, Smith said in a phone interview this week.

"Phages are the world champion at replication. You can drop one filamentous phage particle into a one-liter culture of e. coli bacteria ... and shake it overnight at body temperature in a shaker incubator," Smith said. "The next day there is not one particle, but 10 to the 15th particles. Ten to the 15th is 1,000 trillion particles in just 20 hours of growth."

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Disease or cancer cells are introduced to a phage library, and then Cell Origins or the business they consult with can see which phage book gets "checked out." In other words, to which phage did the disease or cancer cells attach or have an affinity selection.

For one of Cell Origins' current clients, testing of the the phage library returned about 60 hits from the billions of phages in the library.

"We’ll take those 60, test them individually and after that we may have one to five leads that say these are the best ones," Soendergaard said. "From that point, we can start to optimize to make the drug even better or the drug company will take over."

Cell Origins is not set up to conduct clinical trials of a new drug, so it would be up to the pharmaceutical company to establish that with information learned from consulting with Cell Origins.

"Drugs always work by binding to something we already have inside our bodies. That could be a protein, DNA, enzymes, anything like that," Soendergaard said. "Peptides and the antibodies we work with can also do the same thing, but in addition to that, especially with peptides, there is a lot of radiopharmacy going on."

This is where a radioactive metal, also known as a radionuclide, can be included in discovered drugs to directly bind to cancer cells in a tumor, applying radiation directly to a tumor to shrink it from inside a person's body, rather than external radiotherapy.

A growing field and product development

While phage display has been around since Smith started studying it in 1984 as an extension of modern microbiology, which started in the 1940s, its application to drug discovery started an upswing after Smith's Nobel win, Soendergaard said.

"Phage display has always received a lot of attention since he developed it. It’s thousands of research articles. But when someone gets a Nobel Prize, people who may not be as familiar start to look into it too," she said.

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Part of the work of Cell Origins, apart from its phage libraries, is the creation of a test kit with standardized and repeatable results. This is to keep testing consistent despite differing lab conditions.

"Our kit doesn’t include a phage library, but a small number of phage that we have already selected from a library. We filed for a provisional patent last spring and this spring we’re filing the full patent," Soendergaard said. "... The problem with working with human cells or any kind of cell really is you have to be careful treating the cells correctly all the time, because otherwise they start changing."

The plan is to present the kit at various conferences and to pharmaceutical companies for their use. Once patents are secured, Cell Origins will start work on a beta test kit to improve upon the first.

"The idea is that a buyer would purchase a kit and in that we have a genetically-modified phage," Soendergaard said. "They'll be able to tell the difference or verify if the cells they are working with are in a good state. That is our own product we are developing."

Cell Origins wants to grow as a business organically by gaining new clients and not necessarily through capital investments.

"We are not looking for investors, but we are not against it. If we can grow on our own that is what we would prefer to do," Soendergaard said. "Within the next year, we’ll develop the beta version of our own product and have it tested out in other labs throughout the country."

Charles Dunlap covers local government, community stories and other general subjects for the Tribune. You can reach him at cdunlap@columbiatribune.com or @CD_CDT on Twitter. Subscribe to support vital local journalism.

This article originally appeared on Columbia Daily Tribune: Cell Origins, from three MU grads, uses pioneering phage display for drug discovery