New immunotherapy possible for canine cancer

The work extends research by Stanford scientists who found that blocking CD47 might be useful in treating human cancer.

Irving Weissman

Blocking a cell surface protein called CD47 may help treat at least one kind of cancer in dogs, according to a study by researchers at the School of Medicine and other institutions.

The work expands on research by Irving Weissman, MD, professor of pathology and of developmental biology, and his colleagues, who found that blocking CD47 might be useful in treating nearly every kind of human cancer.

The study was published online Nov. 14 in Cancer Immunology Research.

Kipp Weiskopf, MD, PhD, a former student at the School of Medicine, is lead author of the study. Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, and Jaime Modiano, VMD, PhD, of the University of Minnesota, share senior authorship.

‘Don’t eat me’

The CD47 protein acts as a “don’t eat me” signal to immune cells called macrophages, which normally engulf and devour cancer cells and other diseased and dying cells. It turns out that nearly every kind of cancer uses CD47 to evade these macrophages. Covering up the CD47 “don’t eat me” protein allows the immune cells to find and swallow cancer cells. An anti-CD47 antibody is currently in a small, phase-1 clinical trial in cancer patients at Stanford and elsewhere.

We hope that these studies help companion animals and further inform us about treating disease in humans.

Weiskopf and his fellow researchers took canine lymphoma, one of the most common cancers in dogs, and put it into laboratory mice. Weiskopf then injected the mice with CV1, a molecule he helped develop to bind tightly to the CD47 receptor and block the “don’t eat me” signal. In some cases, they also used a specially devised antibody against a protein called CD20 to act as an “eat me” signal to attract immune cells to the cancer.

They found that when anti-CD20 antibody alone was used to treat the dog cancer in mice, none of the mice survived. When CV1 was used by itself to treat the cancer, only 20 percent of the mice survived. But when the anti-CD20 antibody and CV1 molecule were used together, 100 percent of the mice survived with no further evidence of disease. They seemed to be cured.

Leading cause of illness in dogs

Cancer is among the leading causes of illness in dogs, and clinical trials with actual cancer-stricken dogs are the next step. “We hope that these studies help companion animals and further inform us about treating disease in humans,” Weiskopf said.

Weissman noted that it is an important first step that the molecular tools used to target human CD47 also work against dog cancers, at least when tested in a mouse host. “This should provide impetus to produce even more effective anti-CD47 proteins that are designed for optimal targeting of dog — and separately, cat — CD47 molecules and cancers,” he said. Weissman is also director of the Stanford Ludwig Center for Cancer Stem Cell Research and Medicine.

Other Stanford co-authors of the study are graduate student Amira Barkal; former postdoctoral scholar Susan Prohaska; former medical school student Aaron Ring, MD, PhD; and former lab technicians Peter Schnorr and Kelly McKenna.

Researchers from the University of Minnesota, Elanco Animal Health U.S. Inc. and the Genomics Institute of the Novartis Research Foundation also co-authored the study.

The work was supported at Stanford by the National Institutes of Health (grants F30CA168059, F30CA195973, P01CA139490, P30CA077598 and T32GM07365), the Morris Animal Foundation, the Joseph and Laurie Lacob Gynecologic/Ovarian Cancer Fund, Ludwig Cancer Research, the Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, Stanford SPARK, the Skippy Frank Fund for Life Sciences and Translational Research, and an anonymous donors fund.

Stanford’s departments of Pathology and of Developmental Biology also supported the work.

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