Cancer immunotherapy, a groundbreaking approach that trains the body’s own T cells to fight malignancy, holds enormous promise but has historically struggled against tumors like ovarian cancer. While FDA-approved checkpoint inhibitors are effective in “taking the brakes off” the immune system, ovarian tumors create a microenvironment so suppressive that a weak immune response, or none at all, is often launched.

“The problem with ovarian cancer is no one is hitting the gas,” said Ivan Pires, the lead author of the new study and a former MIT PhD student. “So, even if you take off the brakes, nothing happens.”

To address this challenge, researchers from MIT and the Scripps Research Institute developed a novel nanoparticle system designed to deliver a potent immune-stimulating molecule, IL-12, directly to the tumor site. IL-12 acts as the necessary accelerator, supercharging T cells, but in its traditional form, the doses required for efficacy cause severe, generalized side effects.

Nanoparticle Strategy Attacks Ovarian Tumors

The team, led by senior authors Paula Hammond and Darrell Irvine, engineered tiny, fatty liposomes coated with a polymer called poly-L-glutamate (PLE) to specifically target ovarian tumor cells. They developed a new chemical linker to attach the IL-12 payload, ensuring a stable and gradual release over approximately a week. This controlled delivery method allows the immune-booster to work locally while minimizing systemic toxicity.

The results were published in Nature Materials.

In mouse models of metastatic ovarian cancer, a combination of the IL-12 nanoparticles and checkpoint inhibitors eliminated tumors in more than 80% of the animals. Even more compelling, the treatment established a powerful immune memory. When the cured mice were re-challenged with cancer cells five months later, their immune systems cleared the threat immediately.

“We don’t see the cancer cells being able to develop again in that same mouse, meaning that we do have an immune memory developed in those animals,” Pires says.

The mechanism is a clever subversion of the cancer itself.

“What’s really exciting is that we’re able to deliver IL-12 directly in the tumor space,” Paula Hammond, an MIT Institute Professor, 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.”

This study offers a powerful template for overcoming immunotherapy resistance, demonstrating that precise, localized delivery of immune activators can unlock the full potential of cancer-fighting drugs.