Oxford University begins clinical trial of anti-CD47 antibody in the treatment of acute myeloid leukemia

Researchers at Oxford University in the United Kingdom announced that they are beginning a small clinical trial of an innovative anti-cancer therapy developed at the Stanford University School of Medicine. The therapy, an antibody to a protein called CD47, allows the body’s immune system to engulf and devour cancer cells. The clinical trial in the UK is being done in cooperation with Stanford. It will involve a small number of patients with acute myeloid leukemia (AML), and parallels a small, ongoing phase-1 trial of the therapy at Stanford for solid tumors.

“It’s extremely gratifying that a discovery that started here at Stanford is now in clinical trials internationally,” said Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

Years ago, researchers in Weissman’s lab discovered that the CD47 molecule acts as a “don’t eat me” signal to immune cells called macrophages, which normally devour and digest infected, damaged or malfunctioning cells. When comparing leukemia cells with normal cells, the researchers discovered that the leukemia cells covered themselves with CD47 protein, effectively blocking the immune system from attacking them.

Weissman, along with Associate Professor of Medicine Ravi Majeti, MD, PhD and their colleagues at Stanford, then developed an antibody that blocked the CD47 signal and administered it to mice that had been dosed with human leukemia cells. Untreated, the leukemia cells would multiply and kill the mouse. During the first such experiment, however, the antibody enabled the mouse’s immune system to completely wipe out the leukemia cells. The researchers did similar experiments in animals to test the antibody against many other human cancers. In 2014, Stanford began a small phase-1 trial to assess the safety of the therapy in patients with solid cancers.

The human clinical trials of the therapy are unusual, said Weissman, because they are being done under the purview of the universities, without the sponsorship of a commercial pharmaceutical company. This was made possible through the support of the California Institute for Regenerative Medicine and Ludwig Cancer Research, as well as the University of Oxford, the Medical Research Council and the national charity Bloodwise in the UK.

The fact that we are able to do the basic research and carry the science through phase-1 clinical trials is the result of extraordinary funding and support...

“The fact that we are able to do the basic research and carry the science through phase-1 clinical trials is the result of extraordinary funding and support,” Weissman said, who is also the director of the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford.

“This trial is a wonderful example of how two great universities across the Atlantic can come together to work on a completely new class of cancer therapy, taking the basic scientific and pre-clinical observations at Stanford and jointly developing a clinical trial program in blood cancers,” said Paresh Vyas, the Chief Investigator for the trial in the UK. Vyas noted that the experimental therapy potentially addresses a specific huge unmet need in patients with AML, which is the most common aggressive adult leukemia and has high mortality rates, particularly in the elderly. The lack of good therapeutic options for treating AML makes the development of new therapies especially important, he said. “Jointly, we very excited by the potential this trial program may offer to patients and their families.”