Four years ago, Irv Weissman, director of the Ludwig Center at Stanford, and colleagues published a paper showing, in mice, that blocking a cell surface protein called CD47 might be a potent treatment for a wide variety of human cancers. Now his laboratory, in collaboration with the University of Minnesota and other institutions, has shown CD47-blockade could help treat at least one kind of cancer in dogs as well. Their paper appears in Cancer Immunology Research.
CD47 acts as a “don’t eat me” signal to innate immune cells called macrophages that gobble up sick and cancerous cells. Nearly every kind of cancer exploits CD47 to evade such attack, and blocking the protein allows macrophages to find and swallow malignant cells. An anti-CD47 antibody is currently in a small, Phase I clinical trial in cancer patients at Stanford and elsewhere.
In the current study, the researchers took canine lymphoma, put it into specially prepared mice and then injected the mice with a protein designed to bind tightly to the CD47. 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. Clinical trials with actual cancer-stricken dogs are the next step.