Liver cancer is the third leading cause of cancer mortality worldwide and kills more people in Texas than in any other state. Rather than decreasing like many other cancers, the rate of hepatocellular carcinoma has tripled in the last 20 years. Risk factors include obesity, alcohol abuse, and type 2 diabetes, all of which are on the rise.
The disease often has a poor prognosis, and although immune checkpoint therapy can be effective for other cancers, it works poorly in the liver because of the low population of immune cells there.
Now a bioengineer at Rice University is exploring a novel approach to treating liver cancer that has the potential to greatly improve the effectiveness of treatment. Kevin McHugh was recruited to Rice University department of bioengineering from the Massachusetts Institute of Technology, where he was a postdoctoral fellow at the Koch Institute for Integrative Cancer Research. He was recruited in 2019 with the help of a First-Time Tenure-Track Award from CPRIT.
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Liver cancer is the third leading cause of cancer mortality worldwide and kills more people in Texas than in any other state. Rather than decreasing like many other cancers, the rate of hepatocellular carcinoma has tripled in the last 20 years. Risk factors include obesity, alcohol abuse, and type 2 diabetes, all of which are on the rise.
The disease often has a poor prognosis, and although immune checkpoint therapy can be effective for other cancers, it works poorly in the liver because of the low population of immune cells there.
Now a bioengineer at Rice University is exploring a novel approach to treating liver cancer that has the potential to greatly improve the effectiveness of treatment. Kevin McHugh was recruited to Rice University department of bioengineering from the Massachusetts Institute of Technology, where he was a postdoctoral fellow at the Koch Institute for Integrative Cancer Research. He was recruited in 2019 with the help of a First-Time Tenure-Track Award from CPRIT.
One treatment that shows promise is injecting the liver with compounds—called cyclic dinucleotides—that stimulate the innate immune system, drawing T cell lymphocytes to the cancer and inducing them to destroy it. CDNs are currently in clinical trials for a variety of cancers and awaiting FDA approval. But getting these compounds where they need to be and also keeping them active long enough to stimulate a response remain a challenge. Currently, a patient would have to receive multiple injections, which are difficult, painful, and potentially introduce infection.
McHugh is exploring the use of small biodegradable capsules that could be injected once into the liver and release the drug over time. He is developing controlled-release microparticles that encapsulate the CDNs. He’s trying out different types of materials that release their contents at different times. Some of the CDNs would be released after 3 days, another burst at say, 6 days, and so on. So a patient could receive one injection but keep activating the immune system over and over.
McHugh is tackling the problems of how to make a lot of the particles, how to fill them, and how to make them small enough to pass through a catheter or needle. “We also need to evaluate polymers with different properties that release at the time-points that we want,” he says. “If we make this type of particle with CDN in it we have to know that it will always release at 6 days, for example.”
So far, the microparticles are effective in mice. McHugh says he’s well positioned to eventually move his technology into clinical trials, with MD Anderson across the street. He says in the future, the CDN-containing microparticles might be able to be used in conjunction with immune-checkpoint therapy to give cancer a double-whammy. The CDNs recruit immune cells to the liver and immune-checkpoint therapy disables the cancer’s ability to hide from them.
McHugh says having the resources provided by CPRIT accelerates his timeline by a couple of years and facilitates collaborations. “When I call and say I’m a CPRIT Scholar in cancer research that carries some weight in terms of what they think about you as a young investigator,” he says.
McHugh received his undergraduate degree in biomedical engineering from Case Western Reserve University and his Ph.D. in biomedical engineering from Boston University. He began his postdoctoral fellowship at MIT in 2014.
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