A ground-breaking study led by engineering and medical researchers at the University of Minnesota Twin Cities demonstrates how engineered immune cells used in new cancer therapies can overcome physical barriers, allowing a patient’s immune system to fight tumours. The research could lead to better cancer treatments for millions of people around the world in the future.
The study was published in a peer-reviewed, open-access scientific journal, Nature Communications, by University of Minnesota researchers Erdem Tabdanov, Nelson J. Rodrguez-Merced, Vikram Puram, Mackenzie Callaway, and Ethan Ensminger; Emily Pomeroy, Kenta Yamamoto, Walker Lahr, Beau Webber, and Branden Moriarity; and National Institute of Standards and Technology researchers a
Immunotherapy is a type of cancer treatment that uses the patient’s immune system to fight cancer rather than chemicals or radiation. T cells are necessary for the immune system to function properly that are a kind of white blood cell. Cytotoxic T cells serve as soldiers, pursuing and destroying invading cells.
While immunotherapy has successfully treated some types of cancer in the blood or blood-producing organs, the job of a T cell in solid tumours is much more difficult.
“The tumour is like an obstacle course, and the T cell has to run the gauntlet to get to the cancer cells,” Dr. Provenzano explained. “These T cells get into tumours, but they can’t move around well and can’t get to where they need to go before they run out of gas and are exhausted.”
The researchers are developing engineering design criteria for T cells in order to mechanically optimise them or make them more “fit” for overcoming the barriers in this first-of-its-kind study. If these immune cells can recognize and attack cancer cells, they will destroy the tumour.
The stiffness of a tumour’s fibrous mass causes immune cells to slow down by about twofold, almost as if they were running in quicksand.
“This is our first publication in which we identified some structural and signalling elements where we can tune these T cells to make them more effective cancer fighters,” Dr. Provenzano explained. “Each ‘obstacle course’ within a tumour is unique, but there are some similarities. We discovered that after engineering these immune cells, they moved through the tumour nearly twice as fast, regardless of the obstacles in their path.”
The authors used advanced gene-editing technologies (also known as genome editing) to change the T cells’ DNA better to overcome the tumour’s barriers. The ultimate goal is to slow down cancer cells while increasing the speed of engineered immune cells. The researchers are working to develop cells that are capable of overcoming various types of barriers. When these cells are combined, the goal is for groups of immune cells to overcome all of the multiple obstacles to reach the cancer cells.
The next step, according to Dr. Provenzano, is to continue studying the mechanical properties of cells in order to gain a better understanding of how immune cells and cancer cells interact. The researchers are currently conducting rodent studies on engineered immune cells and intend to conduct human clinical trials in the future.
While the initial research has focused on pancreatic cancer, Dr. Provenzano believes the techniques they are developing could be applied to a wide range of cancers.
“Using cell engineering to fight cancer is a relatively new field,” Dr. Provenzano explained. “It enables a highly personalized approach with applications for a wide range of cancers. We believe we are launching a new line of investigation into how our bodies can fight cancer. This has the potential to have a significant impact in the future.”
Erdem D. Tabdanov, Nelson J. Rodríguez-Merced, Alexander X. Cartagena-Rivera, Vikram V. Puram, Mackenzie K. Callaway, Ethan A. Ensminger, Emily J. Pomeroy, Kenta Yamamoto, Walker S. Lahr, Beau R. Webber, Branden S. Moriarity, Alexander S. Zhovmer, Paolo P. Provenzano. Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-22985-5
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