'Plug-and-play' CAR T technology adapts as cancer changes

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by City of Hope National Medical Center

edited by Sadie Harley, reviewed by Robert Egan

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Researchers from City of Hope have developed a new "plug-and-play" technology that adds engineered molecules to chimeric antigen receptor (CAR) T cells after treatment, allowing scientists to better control the cells and redirect them to attack different types of cancer. Credit: City of Hope

Researchers from City of Hope have developed a new "plug-and-play" technology that adds engineered molecules to chimeric antigen receptor (CAR) T cells after treatment, allowing scientists to better control the cells and redirect them to attack different types of cancer. Published in Cancer Immunology Research, the preclinical study offers a more flexible way to help CAR T cells keep pace with mutating tumors.

CAR T cell therapy genetically reprograms a patient's immune cells to seek out and kill cancer. The personalized approach has revolutionized treatment, yet today's therapies remain largely "hardwired" and unable to adapt after the rewired cells are restored to the patient's bloodstream.

"The bottom line is that tumors adapt to CAR T therapies, leading to treatment failure and cancer relapse. To remain effective, our therapies need to adapt, too," said co-senior author John Williams, Ph.D., director of City of Hope's X-ray Crystallography Core. "City of Hope has created a system that allows us to reconfigure these potent cancer killers as the tumor progresses."

A solution to CAR T's drawbacks

While effective at treating blood cancers, CAR T therapies face several limitations. The treatments have short life spans, can cause serious side effects and can't be altered after infusion. As tumors evolve and develop new ways to escape immune attack, CAR T cells can lose their effectiveness, allowing some cancer cells to survive and drive relapse.

To overcome these hurdles, Williams collaborated with co-senior author Christine Brown, Ph.D., deputy director of T Cell Therapeutics Research Laboratories at City of Hope, to build on his earlier research on a technology called meditope, a molecular "docking system" that allows scientists to add new capabilities to immunotherapies.

In the new study, the scientists redesigned CAR T cells so they could connect with a small molecule called meP, creating a new type of cell called meCAR T.

Next, the team showed that meCAR T cells could be equipped with different add-ons that help them be tracked, grow and recognize a wider range of cancer cells.

New platform delivers power and flexibility

"Much like a software update adds new features to a smartphone after you buy it, meditope allows us to send new instructions to CAR T cells already in the body," said Williams, a professor in the Department of Cancer Biology and Molecular Medicine at Beckman Research Institute of City of Hope.

The team also showed that meCAR T cells could be programmed to carry out new functions, helping researchers better control how the cells find and attack cancer.

"The power of this platform is its flexibility," said Brown, City of Hope's Heritage Provider Network Professor of Immunotherapy. "Instead of hardwiring every function into a CAR T cell, we can use protein-adaptor plug-ins to add new capabilities as needed, improving their ability to overcome tumor heterogeneity and other barriers that limit CAR T therapy in solid tumors."

The next step will be to translate the study's promising findings into clinical testing. The researchers are developing two Phase I clinical trials to evaluate the safety and activity of meCAR T cells as a platform for treating patients with solid tumors and acute myeloid leukemia.

"We're excited about this new platform that allows us to control CAR T cells," said Brown. "Our approach potentially could be applied across many different cancers and other diseases for which CAR T cell therapies are being developed."

More information

Cheng-Fu Kuo et al, Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells, Cancer Immunology Research (2026). DOI: 10.1158/2326-6066.cir-25-1285

Key medical concepts

Chimeric Antigen Receptor T-cellsAcute Myeloid Leukemia

Clinical categories

OncologyAllergy and immunology Provided by City of Hope National Medical Center Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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