Antibody aids immunotherapy in clearing out cancer in mice

Immunotherapy is a promising form of treatment against cancer that can have incredible results – when it works. Now researchers at Washington University in St. Louis have found that blocking a certain protein boosts the effectiveness of standard immunotherapy drugs.

With immune cells constantly patrolling our bodies for abnormalities and clearing them out before they get too advanced, our immune system remains our best weapon against cancer. It’s not entirely surprising then that supercharging the immune system has been an effective form of cancer therapy.

The problem is that cancer is a crafty enemy, using a range of tricks to evade the immune system, even when its activity is ramped up. Tumors are known to create an environment around themselves that suppresses T cells and other immune system “soldiers.” One form of immunotherapy, known as checkpoint inhibition, is designed to rouse those sleepy T cells, but it doesn’t always work.

But now researchers have found a way to boost the effectiveness of this type of immunotherapy. They identified a protein called TREM2 that’s expressed in high amounts in and around tumors, and appears to play a key role in immune system suppression. The hypothesis was that blocking this protein could improve immunotherapy outcomes.

Colorized images of four groups of mice that received different cancer immunotherapy treatments
Colorized images of four groups of mice that received different cancer immunotherapy treatments

William Vermi/Martina Molgora

The team tested the idea in mice with sarcoma. One group received an antibody that blocked TREM2, one group received a checkpoint inhibitor, another group received both together, and a fourth group received just a placebo.

As expected, the control group’s cancers grew steadily. The mice that received either treatment alone saw their tumor growth slow down, and in some cases reverse. But strikingly, every mouse that received both treatments together had their cancers completely disappear. Another round of experiments, targeting colorectal cancers, had similar results.

There are a few advantages to TREM2 as a target. For one, the team says that this protein is expressed only in tumors, meaning any treatment engaging TREM2 will be selective for cancer and shouldn’t harm healthy cells. Secondly, the protein has been seen to be expressed in many different types of cancers, so it could be widely applicable. And finally, antibodies against TREM2 are already in clinical trials for other diseases, meaning the road to a potential cancer immunotherapy should have fewer hurdles.

“Essentially, we have found a new tool to enhance tumor immunotherapy,” says Marco Colonna, senior author of the study. “An antibody against TREM2 alone reduces the growth of certain tumors, and when we combine it with an immunotherapy drug, we see total rejection of the tumor. We have to do more work in animal models to verify these results, but if those work, we’d be able to move into clinical trials fairly easily because there are already a number of antibodies available.”

The research was published in the journal Cell.

Source: Washington University in St. Louis

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