EORTC CLTF 2018 | CD47-targeting antibody: targeting the source of non-Hodgkin lymphoma

Irving Weissman

CD47 has been found to be present on leukemic stem cells, but not on normal hematopoietic stem cells, offering an opportunity to target the source of the disease. Here, Irving Weissman, MD, of the Stanford University School of Medicine, Stanford, CA, discusses the use of an anti-CD47 antibody, which has shown promising results in combination with rituximab for follicular lymphoma and diffuse large B-cell lymphoma (NCT02953509). This interview was recorded at the European Organisation for the Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force (CLTF) 2018 Congress, held in St. Gallen, Switzerland.

Transcript (edited for clarity):

I did talk about how do leukemias develop. And to make a very short one within the blood forming system, only the stem cells make more of themselves. A daughter cell that’s not a stem cell has an eight-week lifespan, that’s it! So when you look at cancers or leukemias and you see they have not one mutation that started the disease, but seven, eight, ten, twenty mutations, it could only occur in a self renewing cell. So we showed every human leukemia, everyone we’ve looked at, all of the mutations except the last ones that lead to the leukemia are in a stem cell that expands and expands to take the place of the others.
Because stem cells in the bone marrow make blood, there are different stem cells in the brain that make brain cells, different ones in the breast that make breast cells, different ones in the lung and so on. So we are testing whether that pre-cancer development always occurs in the tissue stem cell. When we compared the genes and the protein on a purified human leukemia stem cell versus the normal stem cell, we found a don’t eat me molecule called CD47. We found if we block that with an antibody, it would be eaten by the scavenger macrophages in the body. And if we add that antibody plus another one like rituximab for lymphoma, we had dramatic experimental responses.
I have a company that I did start, called 47 Inc. I have stock in and I’m a director so I might be biased, but the oncology group, the lymphoma oncology group just reported that the combination of the anti-CD47 antibody and rituximab led to responses in people with large cell lymphoma or follicular lymphoma who could no longer respond to rituximab in chemotherapy. Half of them responded and it looks like 80% of the half or about 40% are in complete remission now for a year to two years, so we’re hoping that this will work because every cancer has a don’t eat me signal. There may be a few don’t eat me signals but CD47 is the dominant one.
So we hope to carry therefore, this field forward. We want to clear out disease cells and immune cells so we can do safe pure stem cell transplants for dread diseases that even young or very old people get and they wouldn’t be able to stand the chemotherapy. And we have I think a handle on understanding how cancers develop.

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