Adoptive Cell Therapy To Fight Tumors

For the treatment of metastatic melanoma, adoptive cell therapy (ACT) has emerged as a viable immunotherapy approach. The method, which uses immune cells extracted from the patient’s own malignancies, may give cancer patients a new choice for treatment by avoiding harsh chemotherapy medications and radiation treatments.
The attack cells of cancers can now be non-invasively isolated from blood rather than tumors, according to researchers at Northwestern University. The discovery enables Adoptive Cell Therapy to treat cancer kinds that are more difficult to reach and makes it a more practical treatment option for hospitals.

“We started asking questions about whether the immune cells that go into tumors come back out, and if you could find them in the bloodstream,” said Shana O. Kelley, the paper’s corresponding author. “We didn’t know if we’d be able to find them or if we could see enough of them to even study them. Sure enough, they’re in the blood. This is the first time these cells have been studied in this context.”

Kelley is a professor of biochemistry and molecular genetics at Northwestern University’s Feinberg School of Medicine as well as the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern University’s Weinberg College of Arts and Sciences and McCormick School of Engineering. She also serves as president of the Chicago-based Chan Zuckerberg Biohub.

The study, which was released today in the journal Nature Biomedical Engineering, expands upon earlier research from Kelley’s lab, which was published in the same publication last year. When compared to conventional cell-therapy techniques, Kelley and her team’s prior study found that giving animals their own immune cells from a mass significantly reduced the size of their tumors.

In addition, a unique technique for isolating and growing tumor-infiltrating lymphocytes (TILs) was described in the 2022 paper. This technique efficiently selects through and harvests cells to recover 400% more than conventional methods, thereby strengthening the anti-cancer response.

TILs have been discovered in melanoma tumors after their removal and processing by researchers. However, sometimes surgically removing tumors in order to collect TILs might put patients at serious risk, blocking attempts to use ACT to treat other cancers.

Kelley questioned whether TILs may exist outside of tumors in other parts of the body.

The team investigated whether circulating tumor-reactive lymphocytes (cTRLs), which resemble TILs, have the same capacity to eradicate tumor cells as TILs after identifying cTRLs in animal blood. Unexpectedly, they did.

To overcome another major stumbling point, after finding and profiling cTRLs, the Kelley lab used its novel technology platform to isolate and then replicate only the best tumor fighters.

Again, cTRLs effectively leveled their competition by engaging in direct, “hand-to-hand” combat with tumor cells.

“Engineering-based tools allow you to do things that open up new areas of biology,” said Shana O. Kelley, the paper’s corresponding author. “We could see using the platform at any major medical center, so you could reach a significant number of patients. The platform we use to capture cells is very fast, which brings the cost down, and medical centers are comfortable handling blood.”

Scientists also found cTRLs not just in melanoma models, but in colon, lung, and breast cancer, each tumor expressing a unique signature that TILs bind to.

The new technology was spun off by Kelley into the health technology company CTRL Therapeutics, which will ask the American Food and Drug Administration to put the platform through clinical trials. “This new breakthrough leads us to ask some exciting questions about how early cTRLs appear in blood,” Kelley said. “Could we diagnose and treat cancer earlier using these cells?”

Additionally, Kelley belongs to the Robert H. Lurie Comprehensive Cancer Center at Northwestern University, the Chemistry of Life Processes Institute, the International Institute for Nanotechnology, and the Simpson Querrey Institute for BioNanotechnology.

Zongjie (Daniel) Wang, a professor in the Department of Electrical and computer engineering at the University of Toronto, was the paper’s first author.

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