New nanoparticles help immunotherapy clear more than 80% of ovarian tumors
MIT scientists have designed nanoparticles that could make cancer immunotherapy work better against ovarian tumors, one of the most treatment-resistant cancers.
The new system delivers an immune-activating molecule called IL-12 directly to tumors, helping the body’s own immune cells fight back.
When tested in mice, the approach wiped out metastatic ovarian cancer in more than 80 percent of cases.
Cancer immunotherapy aims to train the immune system to attack tumors. But ovarian cancer often weakens this response.
Checkpoint inhibitors, a class of drugs that release the “brakes” on immune cells, have worked for some cancers but rarely succeed against ovarian tumors.
“The problem with ovarian cancer is no one is hitting the gas. So, even if you take off the brakes, nothing happens,” said Ivan Pires, lead author of the study and now a postdoctoral researcher at Brigham and Women’s Hospital.
IL-12 can act as that missing accelerator by activating T cells and other immune fighters.
However, large doses of IL-12 cause serious side effects, including inflammation, liver toxicity, and in some cases, death.
The MIT team overcame this problem by attaching IL-12 to nanoparticles that release it slowly inside tumors rather than flooding the body all at once.
Gradual release improves safety
The nanoparticles consist of tiny fatty droplets known as liposomes coated with a polymer called poly-L-glutamate (PLE).
This coating helps them target ovarian tumor cells directly. Using a stable chemical linker called maleimide, the team tethered IL-12 to the liposomes so the molecule would be released gradually over about a week.
“With our current technology, we optimize that chemistry such that there’s a more controlled release rate, and that allowed us to have better efficacy,” Pires said.
The slow, steady release prevented dangerous side effects and kept immune cells active within the tumor environment. In tests, IL-12 nanoparticles alone cleared tumors in about 30 percent of mice.
When combined with checkpoint inhibitors, the success rate rose to more than 80 percent, even in aggressive or drug-resistant ovarian cancer models.
Lasting immune protection
Paula Hammond, MIT Institute Professor and co-senior author of the study, said the design helps the cancer teach the immune system to recognize it.
“What’s really exciting is that we’re able to deliver IL-12 directly in the tumor space,” Hammond said.
“And because of the way that this nanomaterial is designed to allow IL-12 to be borne on the surfaces of the cancer cells, we have essentially tricked the cancer into stimulating immune cells to arm themselves against that cancer.”
The treatment also produced long-term immune memory.
When researchers reintroduced cancer cells months later, the cured mice’s immune systems destroyed them before tumors could grow again.
The MIT team, working with the Deshpande Center for Technological Innovation, is now developing plans to advance this therapy toward clinical use.
Source: Interesting Engineering
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New nanoparticles help immunotherapy clear more than 80% of ovarian tumors