Ravi Majeti, MD, PhD, rips away cancer’s disguise so the body can eat it

“Don't eat me!” That’s what CD47, a protein on the surface of baby blood cells, broadcasts to the immune system as these cells make their maiden voyage from bone marrow to spleen. Without this chemical signal, many normal cells like these could be mistaken for invaders and gobbled up by macrophages, the body’s roving cellular garbage disposals.

Researchers at Stanford’s Institute for Stem Cell Biology and Regenerative Medicine found that leukemia cells also express a lot of CD47. So Ravi Majeti and his team, with the leadership of the Institute’s director Irv Weissman, MD, set out to discover if CD47 was the chemical disguise leukemia cells used to escape detection by the immune system.

Could they get macrophages to go after leukemia cells by silencing CD47’s don’t-eat-me signal? To find out, they injected mice with aggressive human leukemia cells. Then they treated the mice with an antibody Ravi, Irv, and their colleagues developed that blocks CD47’s signal.

It worked. The majority of the mice were cured, and under the microscope, Ravi and his team could actually see macrophages feasting on malignant cells.

Meanwhile, others in Irv’s labs started searching for CD47 in solid tumors and found it almost everywhere they looked. When they replicated Ravi’s methods, they had similar successes against more than 20 types of cancer, including breast, ovary, liver, colon, prostate, bladder, and brain. The antibody shrank or even eliminated these tumors and prevented them from spreading.

And just this spring, Irv’s labs showed silencing CD47 on cancer cells doesn’t just announce their presence to hungry macrophages; it gets killer T-cells to attack them, too. Since T-cells “remember,” this work could make cancer vaccines to prevent recurrence possible.

Ravi and his team were the first to reveal the key role that CD47 plays in cancer and the first to realize the huge therapeutic potential of silencing it. Thanks to a $20 million grant from the California Institute for Regenerative Medicine received at an absolutely critical time, they are about to start clinical trials of anti-CD47 treatments, just seven years after their initial findings. While that may seem like a long time, it’s just a third of 20-plus years it typically takes to translate discoveries into treatments in a commercial setting.

Ravi credits Irv’s encouragement and Stanford’s culture. “We were able to take this all the way from discovery to treatment in record time. We simply couldn’t have done it anywhere else.”