When my sister Patty contracted leukemia in 1966, the doctors did everything they knew how to do. She went into remission, which seemed like a return to health.
But it was an illusion. Inside her blood, some of the cancer cells were killed by the chemo and radiation, but the deadliest ones were not. The microscopic leukemia stem cells (LSCs) did not die. They multiplied, Patty’s remission ended, and there was no escape.
The last time I spoke to her, she was in a coma. I was on the East Coast, three thousand miles away. But her best friend Gloria, later to become my wife, was with her.
They put the phone next to Patty’s ear, and I spoke to her, loudly, told her I was all right now, that I had gotten a job and I was fine.
She came out of the coma, and said: “That’s nice, Donny. I love you.”
And then she died.
“It was like she was waiting to hear from you,” said Gloria, “And then she just slipped away.”
Even now, half a century later, I miss her every day. I wish so much my grandchildren could have known her, and benefited from her kindness and wisdom.
But the leukemia killed her, and I could not even strike it back.
Thanks to the California stem cell program, two international teams of scientists are fighting to cure leukemia.
At the University of San Diego, Drs. Dennis Carson, Catriona Jamieson, and Tom Kipps are cooperating with Canadian scientist John Dick: each country paying its own way.
At Stanford, the legendary Irv Weissman is leading another team, with Ravindra Majeti, Branimir Sikic, and Bruno Medeiros, in cooperation with U.K. scientists Paresh Vyas and Denis Talbot, both at the University of Oxford.
What do the two teams have in common? A new way of looking at cancer: fighting the stem cells “evil twin”, the LSCs.
Think of these Leukemia Stem Cells (LSCs) as little monsters with labels on their backs. These labels, or “surface markers” help the body’s immune system identify cancer cell threats, giving out what Weissman calls “EAT ME” signals. If the immune system detects them, it will send fighting cells (macrophages) to kill and eat them.
Unfortunately, Leukemic Stem Cells they know how to hide. LSCs exude a protein coating known as CD47, which covers the surface marker like a little cloak of invisibility. The immune system cannot find them.
The San Diego team has identified and named one of these LSCs, calling it ROR1.
Tom Kipps invented a “heat-seeking missile”, an antibody called UC961, to go after ROR 1.
What is the difference between the two teams’ approaches? Dennis Carson said of Weissman’s group; “We are developing a poison to attack the leukemia; they are changing the body’s response so it can fight the blood cancer.”
The Stanford team has developed an antibody, HU5F9, designed to peel back the “cloak”, so the microscopic monsters can be detected, and killed.
This may help fight other forms of cancer as well.
As Dr. Weissman puts it:
“We have now demonstrated that HU5F9 is effective at inhibiting the growth of tumors, including (cancers of the) breast, bladder, colon, ovaries and multiple myelomas.”
Both teams are doing well. The San Diego team’s antibody is now called CIRMtuzumab, (emphasis added), named after CIRM. Led by Tom Kipps, Catriona Jamieson and Michael Choi, clinical trials are now recruiting. (identifier NCTO2222688)
The research has had international implications. In Canada, Dr. Dick has “successfully procured industry partnership for an extensive biomarker program for finding prognostic gene signatures in AML and other leukemias.”
How important was the California stem cell program in this process?
“Without CIRM, this program would not have left the starting gate…”—Irv Weisssman, personal communication.