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Triple-negative breast cancer is one of the most aggressive cancers. The name tells the story: It lacks the three main targets that make other types of breast cancers more treatable with powerful therapies.

UCLA researchers have developed a novel therapy that could fundamentally change the treatment plan for this deadly disease. In a study published in the Journal of Hematology & Oncology, the team details how this new type of immunotherapy, called CAR-NKT cell therapy, could attack tumors from multiple fronts while dismantling their protective shields.

Patients with triple-negative breast cancer have been waiting far too long for better treatment options. To finally have a therapy that shows superior cancer-fighting ability – and to be just one step away from clinical testing – is incredibly exciting.”

Lili Yang, senior author, professor of microbiology, immunology and molecular genetics and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA

The therapy uses engineered immune cells called CAR-NKT cells, which can be mass-produced from donated blood stem cells and stored ready-to-use. This off-the-shelf approach offers an immediately available treatment option at a fraction of the cost of current personalized cell therapies, which can soar into the hundreds of thousands of dollars.

A triple threat against a triple-negative cancer

CAR-T cell therapies have transformed treatment for certain blood cancers by turning patients’ own immune cells into precision weapons. However, these therapies have struggled against solid tumors like breast cancer, which employ sophisticated defense mechanisms and constantly evolve to evade treatment.

To tackle these hurdles, the UCLA team’s cell therapy harnesses a rare but powerful type of immune cell called invariant natural killer T cell, or NKT cell. When equipped with a chimeric antigen receptor, or CAR, targeting mesothelin – a protein found on triple-negative breast cancer cells – these potent tumor-fighting cells gain the ability to recognize and destroy cancer through three distinct mechanisms.

The first mechanism uses the engineered CAR to target mesothelin, which is associated with more aggressive, metastatic disease. The second leverages the cells’ natural killer receptors that recognize more than 20 molecular markers, making it nearly impossible for tumors to evade all of them. The third employs the cells’ unique T cell receptor to reshape the tumor microenvironment by eliminating immunosuppressive cells.

“We’re not just targeting one molecular marker on cancer cells – we’re identifying dozens of them simultaneously,” said first author Yanruide (Charlie) Li, a postdoctoral scholar in the UCLA Broad Stem Cell Research Center Training Program. “It’s like attacking a fortress from every direction at once. The cancer simply can’t adapt fast enough to escape.”

When the research team tested the novel therapy on tumor samples from patients with late-stage metastatic breast cancer, the CAR-NKT cells successfully killed cancer cells in every single sample tested, while also eliminating the immunosuppressive cells that tumors recruit as protective escorts.

Engineering universal accessibility

Beyond its multipronged cancer-fighting capabilities, the CAR-NKT platform addresses critical barriers that have limited cell therapy access: manufacturing complexity and cost.

Current cellular immunotherapies require collecting each patient’s immune cells, shipping them to specialized laboratories for genetic modification, then returning the customized product into the patient weeks later – a process that can cost six figures and create dangerous delays for patients with aggressive cancers.

Yang’s team takes a fundamentally different approach. Because NKT cells naturally work with any immune system, they can be mass-produced from donated blood stem cells using a scalable system. A single donation could generate enough cells for thousands of treatments, reducing costs to approximately $5,000 per dose.

One product to tackle multiple cancers

The therapy’s promise extends beyond triple-negative breast cancer. Since mesothelin is also highly expressed in ovarian, pancreatic and lung cancers, the same cell product could potentially treat multiple cancer types that remain difficult to address with current immunotherapies.

“This is really a platform technology,” said Yang, who’s also a member of the UCLA Health Jonsson Comprehensive Cancer Center.

With all preclinical studies complete for both triple-negative breast cancer and ovarian cancer, the team is preparing to submit applications to the Food and Drug Administration to begin clinical trials.

“We’ve walked 99 steps to get here,” Yang said. “We’re missing just one final step to begin clinical testing and demonstrate what this promising therapy can really do for patients.”

Additional authors include: Xinyuan Shen, Yichen Zhu, Zhe Li, Ryan Hon, Yanxin Tian, Jie Huang, Annabel Zhao, Nathan Ma, Catherine Zhang, David Lin, Karine Sargsyan and Yuan Yuan.

The research was supported by the California Institute for Regenerative Medicine, the Department of Defense, the UCLA Broad Stem Cell Research Center, the Wendy Ablon Trust, the Parker Institute for Cancer Immunotherapy, UCLA’s department of microbiology, immunology and molecular genetics, the UCLA Office of the Chancellor and the UCLA Goodman-Luskin Microbiome Center. 

The Trump administration is considering a plan to curb a dizzying array of software-powered exports to China, from laptops to jet engines, to retaliate against Beijing’s latest round of rare earth export restrictions, according to a US official and three people briefed by US authorities.

While the plan is not the only option on the table, it would make good on Donald Trump’s threat earlier this month to bar “critical software” exports to China by restricting global shipments of items that contain US software or were produced using US software.

On 10 October, Trump said in a social media post that he would impose additional tariffs of 100% on China’s US-bound shipments, along with new export controls on “any and all critical software” by 1 November without further details. To be sure, the measure, details of which are being reported for the first time, may not move forward, the sources said.

But the fact that such controls are being considered shows the Trump administration is weighing a dramatic escalation of its showdown with China, even as some within the US government favor a gentler approach, according to two of the sources. US stock indexes briefly extended losses on the news, with the S&P 500 down 0.8% and the Nasdaq 1.3% lower before paring their losses.

The White House declined to comment. The commerce department, which oversees export controls, did not respond to requests for comment.

A spokesperson for the Chinese embassy did not comment on the specific US measures under consideration but said China opposed the US “imposing unilateral long-arm jurisdiction measures” and vowed to “take resolute measures to protect its legitimate rights and interests” if the US proceeds down what it views as a wrong path.

Administration officials could announce the measure to put pressure on China but stop short of implementing it, one of the sources said. Narrower policy proposals are also being discussed, two of the people said.

“Everything imaginable is made with US software,” one of the sources said, highlighting the broad scope of the proposed action. The sources declined to be named because the matter was not public.

The move could disrupt global trade with China, especially for technology products, and could come at a cost to the US economy if fully implemented.

The measure, if adopted, would echo restrictions that the Biden administration imposed on Moscow after its 2022 invasion of Ukraine. Those rules restricted exports to Russia of items made globally using US technology or software. Trump’s Truth Social post came just three weeks before a previously announced meeting with Xi Jinping, China’s president, in South Korea, and a day after China dramatically expanded its export controls on rare earth elements. China dominates the market for such elements, which are essential to tech manufacturing.

In his post, Trump said China’s action, also effective 1 November, represented “a moral disgrace” that would impose controls on “virtually every product they make”.

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But questions have swirled about what Trump meant in his response by “critical software” controls.

While Trump has slapped a series of tariffs on China since taking office in January, he has wavered in his use of export restrictions against Beijing, first imposing strict new curbs on shipments of Nvidia’s AI chips as well as chip design software to China, and later removing them.

China expressed its opposition to a Trump administration rule last month that restricts US companies from shipping goods and technology to companies at least 50% owned by sanctioned Chinese firms. Chinese imports currently face US tariffs around 55%, which could shoot up to 155% if Trump follows through on his threatened tariff hike. But Trump appeared to soften his posture on Beijing following the threats, posting on 12 October: “The U.S.A. wants to help China, not hurt it!!!”