T-cell therapies like Gilead’s Yescarta and Novartis’ Kymriah have generated enthusiasm because of their high response rates in patients with lymphoma and leukemia. But the technology—which involves removing immune-boosting T cells from patients and then engineering them to recognize and kill cancer—has proven difficult to translate to solid tumors.
Researchers from the Massachusetts Institute of Technology believe they’ve found a solution to that problem: nanoparticle “backpacks” that can be attached to T cells. The backpacks are filled with drugs that stimulate the immune system, and they’re showing promise in mouse studies—so much promise that MIT spinoff Torque Biotherapeutics is now planning clinical trials for the treatment in several tumor types, according to a statement.
The team is applying the new technology to a technique called adoptive T-cell therapy, in which the immune-boosting cells are taken directly from patients’ tumors, grown outside the body, and then infused back into the body. The technology has been tried in various tumor types in the past, but it hasn't generated a strong enough immune response. Immune-boosting drugs called cytokines can be injected along with the treatments, but because those drugs stimulate every T cell, they can cause harmful inflammatory side effects.
So the MIT researchers developed nanoparticles that can carry cytokines but that don’t release the drugs until the tumor-specific T cells hit their intended target. The particles consist of a gel made from the cytokine Il-15. A chemical change in the surface of T cells acts as a signal of sorts, prompting the nanoparticle to degrade and release its payload when it reaches the tumor.
"That allowed us to link T cell activation to the drug release rate," said Darrell Irvine, Ph.D., a professor of biological engineering and of materials science and engineering, in the statement. “The drug is most efficiently being released at the sites where you want it and not in some healthy tissue where it might cause trouble."
In 60% of mice whose T cells were engineered to express a target of melanoma, the nanoparticle-armed cells caused the tumors to disappear completely, Irvine and his colleagues reported in the journal Nature Biotechnology. They also discovered that the nanoparticles allowed them to give the mice eight times as much IL-15 than they could if they injected the drug directly into the body. Irvine was the senior author of the paper and a co-founder of Torque.
Torque was founded in Boston last year after raising a $21 million A round. Its founding management team is stocked with biopharma veterans, including chief medical officer Becker Hewes, M.D., formerly of Novartis, and CEO Bart Henderson, who previously founded Rhythm.
Deploying tumor-derived T cells against cancer is considered to be a promising, personalized approach to addressing solid tumors. One idea, being examined at the Ludwig Institute for Cancer Research in Switzerland, involves enriching “highly reactive” tumor-infiltrating lymphocytes (TILs) from ovarian tumors, for example. A University of North Carolina team is developing a CAR-T to treat the brain cancer glioblastoma that zeroes in on a surface protein called CSPG4, and Iovance Biotherapeutics (formerly Lion Biotechnologies) is working on TIL technologies targeting a variety of tumor types.
MIT’s Irvine believes that any tumor type with a “known target”—meaning something the T cells can be programmed to recognize—could be enhanced with the cytokine-carrying nanoparticles. As Torque proceeds with clinical trials of the IL-15-infused cells in solid tumors, Irvine plans to study whether other cytokines may be even better at stimulating T cells to attack cancer.