Nanoparticle-delivered combo boosts cancer immunotherapy

Human T cell
Combining checkpoint inhibitors, which reveal cancer cells to immune T cells, with a T-cell agonist improves the overall T-cell response to cancer. Image: NIAID

Cancer cells often evade immune attacks by displaying proteins that disguise them as normal. Checkpoint inhibitors block these proteins and reveal tumor cells to the immune system, but they don't work for many patients. Now University of North Carolina researchers have found that using nanoparticles can boost the efficacy of cancer immunotherapy treatments.

Senior author Andrew Wang, M.D., likens checkpoint proteins to red traffic lights—they send signals to the immune system's T-cells that prevent them from attacking the body’s healthy cells. Tumor cells present proteins that identify them as cancerous, but may also have checkpoints that mask this and make them appear "normal." Checkpoint inhibitors unmask cancerous cells.

“The inhibitor takes away the red lights, but for T-cells to go, you also need green lights,” Wang said in a press release.

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In fact, there's another type of drug called a T-cell agonist, which activates the immune cells and makes them kill cancer more effectively. In a preclinical study, the researchers bound a checkpoint inhibitor and a T-cell agonist to a nanoparticle so they could deliver both at the same time. They observed improved T-cell stimulation and survival in animal models. They presented their findings at the recent American Association for Cancer Research (AACR) Annual Meeting.

While immunotherapies—which enhance the ability of the immune system to identify and fight cancer—show promise, they don’t work as well in some patients as they do in others. That's why a number of groups are trying to improve and personalize immunotherapy.

Researchers at the University of California, San Diego found that deleting the enzyme LATS1/2 from mouse cancer cells improved the mice’s immune response to cancer. Meanwhile, the NIH’s Cancer Genome Atlas Research Network discovered genetic mutations linking eight types of cervical cancers that aren’t caused by human papillomavirus. This could lead to personalized therapies for these tumors.

Several drug companies are also testing combination immunotherapy treatments in cancer. But the UNC team believes improving the way these combos are delivered to patients could prove essential. “Nanoparticles provide us with a tool to co-deliver different agents to T-cells so they will be activated by both agents at the same time,” said first author Yu Mi, M.D., Ph.D., a postdoctoral research associate at the UNC School of Medicine. “We found that the therapeutic effect of nanoparticles is far better than the mixture of free agents.” 

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