Researcher Tweaks T-Cells for Tumors

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Nallathamby and his team are developing a double-sided nanoparticle. Nallathamby and his team are developing a double-sided nanoparticle.

A new cutting-edge cancer treatment called CAR T-cell therapy—which requires only a single treatment—is curing patients with certain lymphomas and blood cancers, but researchers are struggling to translate the treatment for solid tumors. National Breast Cancer Awareness Month is coming to a close, but University of Notre Dame researcher Dr. Prakash Nallathamby is holding steadfast to his goal of unleashing the power of CAR T-cells for breast cancer tumors—a disease that has taken two members of his family.

“So it’s personal for me,” says Nallathamby, whose grandmother and aunt died battling breast cancer. “That personal side of it has had a huge impact, and it is a great motivator to see what more we can do to fight this disease.”

CAR T-cell therapy, designed for patients who don’t respond to conventional therapy, has been administered to just two Hoosier patients. The therapy involves taking a patient’s T-cells (a type of immune system cell) and changing them in the laboratory, so they’ll attack cancer cells when injected back into the patient.

Experts call it a cure and the next chapter of cancer treatment, “but the only setback so far seems to be that it’s only applicable for different lymphomas and blood cancers,” says Nallathamby, “so if there’s any way we could use this for solid [tumors], that’d be great.”

Nallathamby, a research assistant professor of aerospace and mechanical engineering and affiliated member of NDnano, has made it his mission to translate T-cell therapy for solid tumors and is first taking aim at breast cancer.

“Right now, when CAR T-cells are used against solid tumors, there have been some really bad results with regard to [the T-cells] being so efficient that the whole tumor bursts, and it leads to something called tumor lysis syndrome [in which large amounts of killed tumor cells release their contents into the bloodstream],” says Nallathamby. “Or [T-cells] target healthy tissue, and they can’t be switched off. If [T-cells] attack the heart or lungs, it kills the patient.”

Nallathamby’s strategy centers on a unique nanoparticle that his team has designed to take control of the powerful T-cells. The nanoparticle’s key feature is its double-sided structure; one end is designed to bind to the surface of the tumor, and the other has a special receptor that captures the CAR T-cells, ensuring the T-cells will only attach to the nanoparticle, therefore, attacking the tumor and not healthy tissue.

Nallathamby is using a special category of T-cells, called universal CAR T-cells (uCAR T-cells). These are commercially-available T-cells, instead of the conventional T-cells that need to be obtained from the patient. Nallathamby says current CAR T-cell treatment requires 20 to 30 days, but because universal T-cells are readily available, they can be administered within two to three days.

Finally, Nallathamby says a nano activator is injected, providing even more control over the T-cells. The nano activator “turns on” the uCAR T-cells and the dosage amount dictates their killing power, so they don’t attack the tumor too quickly and trigger tumor lysis syndrome.

Importantly, as the activator is depleted, the powerful uCAR T-cells are “turned off.” The specially-designed nanoparticles will also release their grip on the tumor after three to four days and are naturally flushed out of the body. This double layer of protection ensures the T-cells don’t cause any negative “off target” effects in the body.

While still in the early stages of development, Nallathamby believes the strategy will also translate well for ovarian and prostate cancer. Nallathamby says CAR T-cells—while extremely powerful—must also be harnessed to avoid the negative effects of such might. He’s confident managing CAR T-cells’ use in tumors with his specially-designed nanoparticles could unlock the treatment for many more cancers and patients.

In addition to his personal connection to breast cancer, Nallathamby says he chose the disease because it’s a robust area of research.
Nallathamby says advances in immunotherapy, such as CAR T-cell treatment, are also important because patients can maintain a more normal lifestyle.
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