EORTC CLTF 2018 | Normal and neoplastic stem cells: from discovery to treatments

Irving Weissman

Our understanding of stem cells has improved exponentially since their discovery, transforming our treatment of hematological malignancies and other diseases. Here, Irving Weissman, MD, of the Stanford University School of Medicine, Stanford, CA, discusses the use of stem cell transplantation and gives his perspective on their usage thus far. 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):

So many years ago, we found a way to isolate in pure form, the blood-forming stem cell. It showed that, at least in mice, it could restore the blood formation of a mouse that had received the kind of dose of irradiation that people received in Hiroshima and Nagasaki, that just caused them to die at the lowest dose, so it was blood formation failure.
We found we could transplant those, mouse to mouse and human to human. Because we could purify them, we could get them away from any contaminating cancer cells if you’re transplanting it, from a cancer patient, like with breast cancer that is spread, back to itself. The standard of practice was to just transplant the whole tissue, and the cancer cells with it. But we had cancer-free stem cells, and we published about seven years ago that instead of half of the women with metastatic breast cancer dying at twenty-four months, ours didn’t die, half of them, until ten years. Instead of them all being dead by fifteen years, one third of ours are alive twenty-one years later. I talked to two of them on a documentary.
So, although this should be the therapy for people with metastatic breast cancer, or some kinds of lymphoma or myeloma, it’s not. That’s because a large pharmaceutical company bought the rights to carry it forward, and shut it down because they had many businesses to deal with and they picked the best business.
We’ve gone on to show that we can transplant blood forming stem cells from one person to another and if we eliminate the T cells that are immune cells in the bone marrow or the blood, there’s no reaction of the graft from the donor against host tissues. Everybody who gets a genetically different donor-transplanted bone marrow, or immobilized blood, has graft versus host disease. Usually it’s so severe, they have to be in a sterile setting like a bubble. And they have to be immunosuppressed so it doesn’t kill them. It’s the art of bone marrow transplant that makes that still feasible, but we think it’s not necessary- it’s important for cancer treatments, T-cells can do that.
But if you had sickle cell anemia, or Mediterranean anemia, or severe combined immune-deficiency, or juvenile diabetes, or multiple sclerosis, or lupus, you’d want to have stem cells, blood forming stem cells, making an immune system or blood forming system that doesn’t have the disease. But if you have to have graft versus host disease and drugs for life, it’s not worth the risk.
The final thing on that aspect is we now have made antibodies, one against stem cells, another against T-cells, another against natural killer cells, and one against the don’t-eat-me signal, I’ll tell you soon. And now we have mice that don’t get radiation to have a pure stem cell transplant. And we have four humans with SCID who don’t get radiation to get a stem cell transplant, so all of these things are moving as fast as we can from discovery to the clinic.

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