Engineering Faster, More Agile T Cell Cancer Fighters

Cell therapies use engineered T cells extracted from the patient’s own immune system to rally an attack on tumors. Such immunotherapies have been successful for treating “liquid cancers” such as leukemia, but the physical characteristics of solid tumors make them difficult for engineered cytotoxic T cells to infiltrate and eliminate these masses.

"The tumor is sort of like an obstacle course, and the T cell has to run the gauntlet to reach the cancer cells," said Paolo Provenzano, senior author of a research paper recently published in Nature Communications.

"These T cells get into tumors, but they just can't move around well, and they can't go where they need to go before they run out of gas and are exhausted."

In a first-of-its-kind study, Provenzano and colleagues sought to develop a method of engineering T cells using genome editing technology such that they are able to more effectively penetrate and destroy solid tumors.

"This study is our first publication where we have identified some structural and signaling elements where we can tune these T cells to make them more effective cancer fighters," explained Provenzano.

"Every 'obstacle course' within a tumor is slightly different, but there are some similarities. After engineering these immune cells, we found that they moved through the tumor almost twice as fast no matter what obstacles were in their way."

The team created subsets of specialized engineered T cells, each with unique capabilities for navigating different structural and physiological barriers to get to the malignant cells. They did this by adapting the T cells’ microtubules—building blocks of the cytoskeleton that provide cells with structure and shape—such that the cells can migrate faster and more efficiently into cancerous tissues.

The team continues to take a closer look at the mechanical properties of tumor cells using engineered nanotextured elastic platforms. In this way, they hope to create more targeted approaches to making cell-based immunotherapies more potent for solid cancers.

"Using a cell engineering approach to fight cancer is a relatively new field," commented Provenzano. "It allows for a very personalized approach with applications for a wide array of cancers. We feel we are expanding a new line of research to look at how our own bodies can fight cancer. This could have a big impact in the future."

Sources: Nature Communications, University of Minnesota Twin Cities.