Photo of a plastic heart with a stethoscope wrapped around it.

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Stanford Medicine Scope - February 1st, 2021 - by Krista Conger

A cancer treatment in clinical trials may also reduce the inflammation responsible for atherosclerosis -- the buildup of plaque inside arteries that can lead to heart attack and stroke.

Inklings of the finding were first reported in 2016 by my colleague Bruce Goldman, who ably described how the treatment -- an antibody called anti-CD47 -- works and how it could prevent plaque buildup in mice predisposed to develop cardiovascular disease. Now it appears to have a similar effect in humans.

The study was quite small -- just nine people out of 22 enrolled in a phase-1 clinical trial of anti-CD47 for treatment of the blood cancer non-Hodgkin's lymphoma. But of those nine, eight experienced a significant reduction of vascular inflammation after nine weeks of anti-CD47 treatment.

"Heart disease is by far the leading killer in the world," said Stanford vascular medicine physician Nicholas Leeper, MD. "Right now, we can only treat it by reducing the traditional risk factors such as hypertension or elevated cholesterol. While we suspected that anti-CD47 antibodies might reduce inflammation, we were surprised to see such a striking reduction in so few patients within a few weeks."

Leeper and postdoctoral scholar Kai-Uwe Jarr, MD, published their findings in the New England Journal of Medicine.

Macrophages tackle dying cells

Anti-CD47 antibodies work by binding to and obscuring a "don't eat me" molecule on the surface of cancer cells. That molecule protects the cancer cells from being engulfed and eliminated by immune cells called macrophages. The pathway was first worked out in the laboratory of Stanford stem cell biologist Irving Weissman, MD, and anti-CD47 antibodies are in clinical trials for the treatment of many types of cancers.

Recently, Leeper and Weissman showed that atherosclerotic plaques start in much the same way as cancers, when a single smooth muscle cell precursor in the lining of a blood vessel divides repeatedly to make a bump that impinges on blood flow and promotes inflammation.

Because macrophages also remove inflamed and dying cells, Leeper and his colleagues wondered whether the anti-CD47 treatment would affect the patients' levels of vascular inflammation. Early experiments in mice suggested it might. Fortunately, an imaging technique used to identify cancer growth and metastasis can also be used to monitor inflammation in coronary arteries.

Reducing inflammation

The researchers found that eight of the nine lymphoma patients in the trial also had pre-existing atherosclerosis. After nine weeks of treatment with anti-CD47 antibodies, eight of the nine showed a reduction in their levels of inflammation in their coronary arteries -- suggesting that the treatment also helped the macrophages scavenge the cells responsible for damaging plaque.

Although the results are suggestive, more research needs to be done. The patients in the study weren't randomized, and there was no placebo arm. In addition to anti-CD47 antibodies, the participants also received another common lymphoma drug called rituximab.

But the idea of using anti-CD47 antibody to treat heart disease is intriguing.

"The concept of this is truly independent from everything else we can currently offer to patients with cardiovascular disease," Leeper said.

Originally published at Stanford Medicine News Center