Fast technique of isolating tumor-targeting T cells might propel personalised most cancers remedy

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Rapid method of isolating tumor-targeting T cells could propel personalized cancer treatment

A cell infused with a special enzyme interacts with a tumor-targeting immune cell – a process by which the immune cells can be easily detected and used for cancer treatment. Photo credit: Courtesy of Scripps Research's Wu Lab

When it comes to defeating cancer, some immune cells are more powerful than others. But even the best trained eye and today's advanced scientific tools have trouble distinguishing the strongest tumor-fighting cells from the rest.

A new technique developed by scientist Peng Wu, Ph.D., at Scripps Research, aims to change this. It offers a new platform that can advance personalized cancer treatments that have been hampered by the challenges of isolating the most useful immune cells in patients. The development will be published in Cell on October 22nd.

"With many new and emerging personalized cancer therapies, the key to success is finding the sometimes elusive T cells that target the tumor directly, then creating more of those cells outside the patient's body and reintroducing them for tumor treatment . " says Wu, associate professor in the Department of Molecular Medicine and lead author on the study. "With our simple method of detecting and isolating tumor-reactive immune cells, I hope we can advance personalized immunotherapy treatments that are now either too costly or too laborious to achieve."

The method is called FucoID and is named after the enzyme fucosyltransferase, which plays a major role in "marking" the surface of sought immune cells so that they can be seen and captured. The enzyme is loaded onto dendritic cells, a type of immune cell that presents tumor-specific material to the desired T cells. When the cells interact, the enzyme transfers a tag to the tumor-fighting cells so that scientists can use a fluorescent probe to detect it and extract it from the sample.

In experiments with mice, the approach successfully identified several types of so-called "tumor antigen-specific T cells", including CD4 + and CD8 + T cells, which infiltrate tumors and attack them from within. These cells are central to certain cancer immunotherapies – including checkpoint inhibitors and treatments known as adoptive TIL (tumor infiltrating lymphocyte) transfer therapies.

"This approach removes a significant barrier to studying tumor-specific T cells and will be of great benefit to both basic researchers and clinicians," said John Teijaro, Ph.D., associate professor in the Department of Immunology and Microbiology and co-author of the study.

"This study also shows how the highly collaborative environment at Scripps Research drives innovative solutions to unsolvable problems."

The FucoID process to isolate the relevant cells takes only a day, according to Wu, compared to four or five weeks using current methods. "Once we isolate it, we can expand it into millions or billions of cells to construct a treatment or simply to study it," he says.

The ability to quickly take an inventory of these cells in a patient can also help doctors predict therapy success or progress, he says. And doing all of these things faster than today's bioinformatics or genetic manipulation methods can make a big difference to patients.

Wu is now working with clinicians at UC San Diego to use FucoID to isolate the desired T cells from tumor samples from human patients, with the goal of eventually applying the platform to a clinical trial for cancer treatment.

"We believe FucoID has the potential to translate into a clinical setting for the detection and isolation of tumor-reactive immune cells, ultimately paving the way for reducing the cost and accessibility of personalized cancer care," said Wu.

New compounds show how cancer evades the immune system

More information:
Zilei Liu et al., Detection of tumor antigen-specific T cells by interaction-dependent fucosyl biotinylation, Cell (2020). DOI: 10.1016 / j.cell.2020.09.048

Provided by
The Scripps Research Institute

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