There were an estimated 18 million cancer cases around the world in 2020. Though treatment methods have improved greatly in recent years, there is still a long way to go in combatting many types of cancer.
“Right now we don’t have a cure for everything,” said Mei Lin (Ete) Chan, an assistant professor in biomedical engineering in the College of Engineering and Applied Sciences. “But CAR-T cell therapy is a very special cancer treatment with a lot of possibilities.”
Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly evolving immunotherapy that has the potential to revolutionize cancer treatment. However, it remains limited by prohibitively long ex-vivo expansion periods and potential loss of effector function in vivo. Chan is part of a team working to improve CAR-T immunotherapy by shortening cell expansion ex vivo and making it more cost effective, accessible and timely for patients in need. Their promising preliminary work was supported by the seed funding from the Research Evaluation and Commercialization Hubs (REACH) under the National Institutes of Health (NIH).
Chan and her co-principal investigator Clinton T. Rubin, SUNY distinguished professor and director of the Center for Biotechnology, received the 2022 SUNY Technology Accelerator Fund (TAF) Award for their proposal, “Low Intensity Vibration to Accelerate T-Cell Proliferation in Autologous Cell Therapy.” The project aims to test the effectiveness of low-intensity vibration (LIV) in reducing the overall ex-vivo CAR-T cell expansion time by 25 percent without significant changes in activation or functionality.
TAF strategically invests in SUNY’s most disruptive innovations to accelerate their development and commercialization.
“We are committed to translating our basic science to the bedside, coming up with new interventions to help patients recover more quickly and effectively,” said Rubin.
With CAR-T immunotherapy, doctors modify the patient’s own blood to improve their immune cells in the lab, and then inject them back into the patient so they can use their own blood cells to help fight the cancer. Various bioreactors have been developed to address this, but they are expensive and have the limitation of low starting cell density. This delays the initial cell expansion process and can exclude severely lymphodepleted cancer patients.
“After the blood is taken from the patient and the T cells are taken out, CAR can be added,” said Chan. “It’s the secret weapon that we can put on T cells to allow them to find out where the cancers are in the body. Sometimes the cancer cells are so elusive that your own immune system can’t attack them anymore. So they need a little bit of help from researchers.”
Through genetic engineering, researchers put chimeric antigen receptor on the surface of T cells so that when they are reintroduced back into the body, they are more capable of recognizing and attacking cancer cells. Currently available methods are not efficient.
“After all the genetic engineering and purification processes, the CAR-T cell numbers are so low that they have to be expanded,” said Chan. “To do that you have to grow them ex vivo from a very small number of cells. This can take two or three weeks. Patients who are really sick can’t wait that long. What we are trying to do in our lab is make this process faster.”
To do this, Chan and the research team are leveraging the mechanoresponsive mechanism of mammalian cells via LIV, which was developed as a mechanical regime to improve the speed and efficacy of CAR-T cell proliferation without hampering functionality in a non-pharmacologic manner.
“LIV is a high-frequency, low-magnitude sinusoidal mechanical signal,” said Chan. “Our prior work demonstrated that LIV signal parameters can be optimized with our custom-designed system to effectively augment human T cell proliferation under sterile conditions, for example, a 50 percent increase in five days.”
For the team, research that began during the COVID pandemic has now delivered promising data and the possibility of patents and working with industry. These were made possible with the support of the Center of Biotechnology’s NIH-REACH program, Intellectual Property Partners (IPP) and a dedicated team of undergraduate and graduate research students.
“As an MD/PhD student I’ve always been drawn to conducting translation research that can actually be used to improve the lives of patients,” said Christopher Ashdown, a key current team member supported by the Snyder Scholars Program and Medical Scientist Training Program (MSTP). “My project, exploring the effect of vibration on T cell growth and function, is incredibly exciting because it could help to improve existing treatments like CAR-T therapy and give more options to people suffering from cancer.”
“It’s typically two to three years for our part, and then it will require more validation and testing,” said Chan. “But working with a company that’s interested could potentially accelerate that. So maybe instead of 10 years, it could be three or four. We’re not doing this just for publication — we want it to become something a patient can use in the not-too-distant future.”
– Robert Emproto