New immunotherapy technique describes T cell receptors with 100% specificity for individual tumors within a few days; this allows doctors to rapidly create individualized cancer therapies that would allow standard cancer drugs to target tumors effectively without side effects.

A new immunotherapy screening prototype developed by the University of California, Irvine researchers were able to create individualized cancer therapies that would allow physicians to target tumors effectively without the side effects of standard cancer drugs.

Weian Zhao from UCI and Nobel laureate David Baltimore, developed a monitoring and screening system that, within a few days, identified T cell receptors with 100% specificity for individual tumors.

In the human immune system, there are molecules on the surface of T cells that bind to the antigens on the surface of foreign cells or cancer cells. To treat a tumor with T cell therapy, researchers should define exactly which receptor molecules work against antigens of a particular tumor. UCI researchers accelerated this identification process.

“This technology is particularly exciting because it eliminates the huge challenges in cancer treatments,” said Zhao, a professor of pharmaceutical sciences. The use of this droplet microfluidic screening significantly reduces the cost of making new cancer immunotherapies associated with less systemic side effects than standard chemotherapy drugs and greatly accelerates the time frame for treatment.”

He added that traditional cancer therapies offer a one-dimensional disease response, such as chemotherapy drugs, which can lead to systemic and serious side effects.

Steve Zylius / UCI

T-cell therapy, which is driven by a more recent technology, the T cell receptor (TCR), uses the patient’s own immune system to attack tumors. On the surface of cancer cells, the body’s immune system contains antigens, protruding molecules recognized by T cells. This novel treatment places molecules that are engineered on T cells designed to bind cancer cells to cancer cell antigens and allow the T cell to destroy the cancer cell. TCR treatment can be individualized, so each patient can have T cells specifically designed for tumor cells.

This antigen-TCR recognition system is very specific - hundreds of millions of different TCR molecules. A major challenge for TCR-T cell therapy development is to identify specific TCR molecules from millions of probabilistic ponds. Finding a match can take up to a year (when many cancer patients do not have it) and can cost half a million dollars or more per treatment.

However, using tiny cubes of oil-water droplets, Zhao’s team designed a device that allows individual T cells to participate in cancer cells in microscopic liquid containers. TCRs that bind with antigens of cancer cells can be sorted and identified in days rather than months or years needed by prior technologies. Technology also significantly reduces the cost of making individualized TCR, and TCR-T cell therapy accelerates the pipeline to the clinic.

By establishing a partnership with Amberstone Biosciences, which is the beginning of a UCI, the entire platform and screening process will be offered to pharmaceutical companies for drug development in just a few months. This technology not only helps to modify TCR-T cell therapies for cancer, but will also be a powerful tool to discover other immunological agents, including antibodies and CAR-T cells, and to elicit in depth the inability of new immunology and cancer biology.