VivoSphere’s Patented Tissue Engineering Technologies Drive Scalable Production of Cancer Tissues for Disease Modeling and Therapeutic Drug Testing

Auburn NVA company creates a cost-effective, precise test bed for high-throughput, pre-clinical evaluation of critical cancer therapy candidates

Pharmaceutical companies around the globe spend billions of dollars each year to discover, develop and test the efficacy of a wide range of promising therapeutic drugs for devastating cancers impacting tens of millions of people. One component of that cost is embedded in the pre-clinical testing process that pharmaceutical companies go through before deciding to advance any promising drug or therapy candidate to human testing. An even larger component of that cost, however, comes from failures of candidates that move on to the clinical trial stage.

The challenge for pharmaceutical companies is determining which candidates will fail as early as possible in the development and testing process – identifying effective, non-toxic drug candidates during preclinical testing stages while also finding out which are either not effective or toxic and eliminating them from consideration for human testing in the clinical trial stage.

That’s critical because according to research published by the National Institute of Health (NIH), less than 4 percent of oncology candidates undergoing clinical testing succeed, meaning that billions of dollars in cancer research funding is written off as part of the cost of doing business in developing those very few, very valuable therapies. As a result, according to NIH, the median cost of developing a single FDA-approved cancer drug was $648 million in 2017 – and rising.

How They Decide

We sat down with the co-founders of VivoSphere – Drs. Elizabeth Lipke and Yuan Tian – to understand how their patented approach to pre-clinical testing of promising cancer treatments is enabling pharmaceutical companies to better assess which candidates warrant human trials and what that could mean for better patient outcomes going forward.

Lipke, the Mary and John H. Sanders Professor in Auburn’s Department of Chemical Engineering at the Samuel Ginn College of Engineering, and Tian, a post-doctoral researcher in the department, co-founded their biomedical company in 2022 following a 2021 National Science Foundation-awarded project, “I-Corps: Spheroidal engineered tissues for more efficient drug discovery.” The start-up won first place and $25,000 in Alabama Launchpad’s Cycle 2 concept stage finals in August at Auburn University’s New Venture Accelerator.

NVA:       Let’s start with the problem you are trying to solve – why are current methods for conducting pre-clinical trials of promising cancer drugs inadequate?

Lipke:      The challenge is two-fold – create an environment for cancer tissue testing that more closely resembles real-life cancer tissue characteristics while also dramatically expanding the number and types of cancer cells available for testing.

Current approaches are severely limited in terms of both quality and throughput. In today’s two-dimensional test beds, the small sample size in a high throughput setting often offers insufficient number of cells, therefore failing to generate adequate levels of confidence in the results, while existing three-dimensional test beds typically have lower throughput.

Tian:       A major cause of this problem is that traditional drug testing methods involve using flat 2D cell cultures in a dish. But here’s the catch: cancers don’t grow in isolation. Tumors exist within complex 3D environments, interacting with neighboring cells and their surroundings.

We utilize tissue engineering technology to replicate these conditions by creating miniature versions of human tissues, allowing researchers to study the intricate interactions between cancer cells, normal cells, and the extracellular matrix. This level of detail is simply impossible to achieve with 2D cultures.

What’s more, our technology also enables rapid and scalable production of these human-mimicking tissues. This enables a large amount of cancer tissues to be tested in a high-throughput manner, helping the candidates that will eventually fail to “fail fast” while moving those most viable to move to human clinical trials.

NVA:       Can you walk us through how that scientific research turned into an idea for the practical application of your findings in the real world?

Lipke:      To make an impact on the success of cancer therapies, I decided that we should move towards something that was more reproducible. We were looking to develop a way to encapsulate lots of cells at very high density into engineered tissues very, very quickly in order to use them for testing regenerative medicine applications.

               Yuan had just joined the lab as a first-year graduate student, and at that time we were testing different designs of our microfluidic system – including the one that we are now using to produce these spheroidal engineered tissues.

Tian:       The project I was working on was trying to scale production of cells for injectable cell delivery using our newly designed microfluidic device that leverages a molding approach to generate more flexibility in controlling the final products. We filed a patent on this technology through the IP Exchange in collaboration with Dr. Troy Brady.

The Lipke Lab already has another patented technology related to stem cell-based cardiac tissue generation that has great potential when combined with our patent, so now we have two key technologies that can be integrated, and they’re both patented. That’s a great advantage for us because people are moving from small molecules to biological molecules while cell therapies and regenerative medicine are growing rapidly.

NVA:       With what appears to be a broad range of applications for VivoSphere’s technologies, it would appear addressing all of these at once would be a heavy lift for a small start-up, right? Which of these are you focusing on first?

Tian:       So far, we have identified four major applications. The first one is cancer modeling for drug testing, which is the one I was talking about at Launchpad. The next one is regenerative medicine – stem cell-derived heart muscle cells for heart muscle repair. The third one is injectable cell delivery, which is work being done in collaboration with the vet school here, the equine model we’ve been working on. The last one is 3D bioprinting of tissues and organs using the spheres as building blocks, like Legos, where we use small pieces to make bigger pieces.

All of these are very promising, but each has challenges. The biggest challenge for all but one of these is gaining Food and Drug Administration (FDA) approval for use in humans. Cancer modeling for drug testing doesn’t require FDA approval because it won’t be tested in humans, it will be used by pharmaceutical companies to test their drug candidates prior to submitting the most promising of them to clinical trials in humans.

That’s the main reason we decided to go for cancer cell modeling as our first commercial application. In the meantime, we are keeping the research going on all of the other applications. Our strategy is to progress our cancer modeling product line and take what we learn from this first commercialization process to identify the next applications we want to take on, recognizing they will take longer to get to market – primarily because of the requirement for FDA review and approval.

Lipke:      We’ve chosen to focus on colorectal cancer as the specific cancer we’re designing our model to address first because it is one of the deadliest cancers and one that’s likely to be recurrent. It’s a problem that’s increasing, particularly in young and middle-aged adults – before the age of 55. These are people that have families, they’re raising their kids. They have a long life ahead of them and we need to have better treatments for these people.

NVA:       So, we’ve covered some of the accuracy advantages of your cancer cell modeling application, can you talk more about the throughput aspect, how that works and why it matters?

Lipke:      With any type of model that you build, whether it’s an animal model or a human cell-based model in vitro, certain aspects of that model are more important than others. One way to look at it is airplane design – the aerodynamics can be modeled without worrying about the seats inside the plane, for example. Not at first, at least.

               We need to set the key success parameters up front so that we don’t make the model too complex. What aspects are critical to answering the questions pharmaceutical companies have and which are only ancillary? If the model you come up with has too many variables, it is difficult to replicate these environments consistently, lowering throughput.

               When we think of throughput, it isn’t how fast these tests can be done, but whether there is enough evidence – enough cell interaction – during these tests to arrive at a defensible conclusion. This means we need a lot of cells and we need to test these interactions for longer periods of time than current methods allow.

Take protein expression, for example – how cells change protein expression in response to a given therapeutic. When you have a small cell culture with only a tiny surface area at the bottom as in 2D cultures, you don’t have enough cells to look at to see what happens. But with our 3D system, instead of putting 5,000 cells into the test well, we can put in 50,000 or more. And we can test these interactions over longer periods of time – weeks or even months instead of merely hours or days. That makes each test more accurate and more valuable to decision-making.

Tian:       We plan to use the rapidly growing database we’re creating to identify patterns of efficacy in tested patients that we can match with other patients presenting similar indications to see the drug response to be expected – to get a better idea of whether this or that particular medicine is going to work for that individual. This is important as we move towards more personalized medical therapies.

NVA:       How is the role you are both now playing as founders of a start-up different from your roles as research scientists and how has the NVA helped with that evolution of roles and responsibilities?

Lipke:      For me, understanding what goes into a strong, defensible patent and how to leverage that intellectual property has been key – making sure that we’re all buttoned up in that fundamental aspect. It is critical to our success.

               To that point, the advice and counsel that we’ve gotten from the New Venture Accelerator in terms of what it takes to go from a unique discovery to a commercially viable product to actually being able to present the value of what we have to those who we need to partner with to succeed cannot be overemphasized.

Tian:       Like Dr. Lipke, I’m a scientist, an engineer, and we like to stay in the lab instead of talking to people who might not understand what it is we do every day. But to be an entrepreneur, I need to get out of my comfort zone, challenge myself.

               I first met with Lou Bifano and Jennifer Nay, and at those first couple of sessions I learned about all the new things I needed to consider, immerse myself in – things I never would have thought about. The guidance we’ve both received from the NVA and all the other entrepreneurial organizations here in Auburn and across Alabama really helped us grow into this new role. Their support in guiding us through all the challenges of establishing strong partnerships, to be a good partner, has been – and continues to be – indispensable.