CD47 or “CDog47”?—New immunotherapy possible for canine cancer

Four years ago, Irv Weissman’s lab at Stanford’s Institute for Stem Cell Biology and Regenerative Medicine published a paper showing that, in mice transplanted with human cancers, blocking a cell surface protein called CD47 might be useful in treating nearly every kind of human cancer. Now, researchers from Stanford, in collaboration with the University of Minnesota and other institutions, have shown that blocking the CD47 receptor can be a potent part of treating at least one kind of cancer in dogs. They published the research today in the journal Cancer Immunology Research. Former Stanford medical student Kipp Weiskopf, MD, PhD, is lead author on the paper. Co-senior authors on the paper are Irv Weissman, MD, who is director of the institute, and Jaime Modiano, VMD, PhD, of the University of Minnesota.

The CD47 protein acts as a “don’t eat me” signal to innate immune cells called macrophages 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 I clinical trial in cancer patients at Stanford and elsewhere.

Lead author Kipp Weiskopf, MD, PhD,  and colleagues took canine lymphoma, one of the most common cancers in dogs, and put it into specially prepared mice. Weiskopf then used CV1, a molecule he helped develop to bind tightly to the CD47 receptor and block the “don’t eat me” signal. In addition, in some cases they used a specially devised antibody against a protein called CD20 to act as a positive “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% of the mice survived. But when the anti-CD20 antibody and CV1 anti-CD47 molecule were used together, 100% of the mice survived with no further evidence of disease. They seemed to be cured.

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,” says Weiskopf.

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

Weissman noted that it is an important first step that the molecular tools that are 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.”

The research involved investigators at the Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford’s Ludwig Center for Cancer Stem Cell Research and Medicine, the Stanford Cancer Institute, the Stanford Department of Molecular and Cellular Physiology, the Stanford Department of Structural Biology, the University of Minnesota, Elanco Animal Health US, Inc., and the Genomics Institute of the Novartis Research Foundation.

Other Stanford research involved in the study include graduate student Amira Barkal, former postdoc Susan Prohaska, former medical student Aaron Ring MD, PhD; and former lab technicians Peter Schnorr and Kelly McKenna.

The work was supported at Stanford by the Joseph & Laurie Lacob Gynecologic/Ovarian Cancer Fund, Ludwig Cancer Research, an Anonymous Donors Fund, the Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, the Stanford Medical Scientist Training Program (T32 GM07365), the Stanford University SPARK Program, and the Skippy Frank Fund for Life Sciences and Translational Research.