T cell receptor therapy, known as TCR therapy, is a form of cancer treatment that genetically modifies immune cells called T cells so they can recognize and attack cancer with high precision. The approach resembles CAR T-cell therapy, but there is an important difference. CAR T-cell therapy can recognize proteins that naturally sit on the outside of cancer cells.
TCR therapy can go deeper. It can detect small pieces of proteins that originate inside a cancer cell and are then transported to the cell surface, where they act like identifying tags. That expanded reach could be especially important for treating solid tumors.
Many of the molecular changes that make these cells cancerous are found inside the cell rather than on its exterior, putting them beyond the reach of many existing immune therapies. Despite its potential, TCR therapy faces a major practical obstacle. Current approaches generally require a personalized treatment made from each patient's own T cells.
Producing those cells can take weeks, and the cost can climb well into six figures. Scientists have investigated another possibility: using T cells from healthy donors to create treatments ahead of time that could be stored and given to many different patients. But donor cells introduce another danger.
They can cause graft-versus-host disease, a potentially serious condition in which the transplanted immune cells mistakenly attack the patient's healthy tissue. Researchers at UCLA say they have developed a strategy that could address both problems at the same time. In a study published in Cell Reports Medicine, the scientists describe a scalable method for making consistent batches of cancer-targeting T cells from blood stem cells obtained from donated cord blood.
The cells are engineered to recognize a protein that appears in many types of solid tumors. When tested in mouse models of ovarian cancer and melanoma, a single dose of the engineered cells, known as AlloESO-T cells, controlled tumor growth and helped the animals survive longer without producing dangerous side effects. "This platform brings us closer to a future where the product is already made, frozen and ready to go as soon as the patient needs," said co-senior author Lili Yang, a professor of microbiology, immunology and molecular genetics and a member of the UCLA Broad Stem Cell Research Center and the UCLA Health Jonsson Comprehensive Cancer Center.
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