At MIT, a few scribbles on a whiteboard can turn into a potentially transformational cancer treatment.
This scenario came to fruition this week when the U.S. Food and Drug Administration approved a system for treating an aggressive form of bladder cancer. More than a decade ago, the system started as an idea in the lab of MIT Professor Michael Cima at the Koch Institute for Integrative Cancer Research, enabled by funding from the National Institutes of Health and MIT's Deshpande Center.
The work that started with a few researchers at MIT turned into a startup, TARIS Biomedical LLC, that was co-founded by Cima and David H. Koch Institute Professor Robert Langer, and acquired by Johnson & Johnson in 2019. In developing the core concept of a device for local drug delivery to the bladder - which represents a new paradigm in bladder cancer treatment - the MIT team approached drug delivery like an engineering problem.
"We spoke to urologists and sketched out the problems with past treatments to get to a set of design parameters," says Cima, a David H. Koch Professor of Engineering and professor of materials science and engineering. "Part of our criteria was it had to fit into urologists' existing procedures. We wanted urologists to know what to do with the system without even reading the instructions for use. That's pretty much how it came out."
To date, the system has been used in patients thousands of times. In one study involving people with high-risk, non-muscle-invasive bladder cancer whose disease had proven resistant to standard care, doctors could find no evidence of cancer in 82.4 percent of patients treated with the system. More than 50 percent of those patients were still cancer-free nine months after treatment.
The results are extremely gratifying for the team of researchers that worked on it at MIT, including Langer and Heejin Lee SM '04, PhD '09, who developed the system as part of his PhD thesis. And Cima says far more people deserve credit than just the ones who scribbled on his whiteboard all those years ago.
"Drug products like this take an enormous amount of effort," says Cima. "There are probably more than 1,000 people that have been involved in developing and commercializing the system: the MIT inventors, the urologists they consulted, the scientists at TARIS, the scientists at Johnson & Johnson - and that's not including all the patients who participated in clinical trials. I also want to emphasize the importance of the MIT ecosystem, and the importance of giving people the resources to pursue arguably crazy ideas. We need to continue to support those kinds of activities."
In the mid 2000s, Langer connected Cima with a urologist at Boston Children's Hospital who was seeking a new treatment for a painful bladder disease known as interstitial cystitis. The standard treatment required frequent drug infusions into a patient's bladder through a catheter, which provided only temporary relief.
A group of researchers including Cima; Lee; Hong Linh Ho Duc SM '05, PhD '09; Grace Kim PhD '08; and Karen Daniel PhD '09 began speaking with urologists and people who had run failed clinical trials involving bladder treatments to understand what went wrong. All that information went on Cima's whiteboard over the course of several weeks. Fortunately, Cima also scribbled "Do not erase!"
"We learned a lot in the process of writing everything down," Cima says. "We learned what not to build and what to avoid."
With the problem well-defined, Cima received a grant from MIT's Deshpande Center for Technological Innovation, which allowed Lee to work on designing a better solution as part of his PhD thesis.
One of the key advances the group made was using a special alloy that gave the device "shape memory" so that it could be straightened out and inserted into the bladder through a catheter. Then it would fold up, preventing it from being expelled during urination.
The new design was able to slowly release drugs over a two-week period - far longer than any other approach - and could then be removed using a thin, flexible tube commonly used in urology, called a cystoscope. The progress was enough for Cima and Langer, who are both serial entrepreneurs, to found TARIS Biomedical and license the technology from MIT. Lee and three other MIT graduates joined the company.
"It was a real pleasure working with Mike Cima, our students, and colleagues on this novel drug delivery system, which is already changing patients' lives," Langer says, "It's a great example of how research at the Koch Institute starts with basic science and engineering and ends up with new treatments for cancer patients."
The FDA's approval of the system for the treatment of certain patients with high-risk, non-muscle-invasive bladder cancer now means that patients with this disease may have a better treatment option. Moving forward, Cima hopes the system continues to be explored to treat other diseases.
