THE BLOG

Fighting the Killers: California Stem Cell Program Takes on Leukemia and Cancer

09/20/2013 05:31 pm ET | Updated Nov 20, 2013
  • Don C. Reed Sponsor, California’s Roman Reed Spinal Cord Injury Research Act of 1999

I was helpless when my sister Patty died, three thousand miles away. The only connection between us was a faintly buzzing phone line.

"She's in a coma," my Mother said, "She can't hear you."

"Put the phone by her ear," I said, and spoke loudly.

"Patty, it's me. I am okay now, I have a job, I am fine."

Silence for a moment, then softly:

"That's nice, Donny," she said, "I love you."

And then she died. She was 23 years old, in a hospital, surrounded by doctors, and there was nothing anybody could do.

It was leukemia. Even now, half a century later, this vile cancer of the blood is still incurable. Despite the most aggressive treatment, patients with Acute Myeloid Leukemia (AML, the kind that took my sister) have only about a 30 percent survival rate. When it comes back after remission, there is only a 10 percent chance of living.

But thanks to dedicated scientists and the California stem cell program, we now know the nature of the enemy: and perhaps a way to defeat it.

The strongest weapon of the California Institute of Regenerative Medicine (CIRM) is the Disease Team grant. To be eligible for these major awards (as much as $20 million each) California scientists set up a dream team to tackle a major disease, develop a plan to challenge the previously incurable condition -- and bring it to human trials within four years.

Two disease teams are taking on leukemia: one from Stanford, the other from the University of California at San Diego. On the UCSD team, Drs. Dennis Carson, Catriona Jamieson, and Tom Kipps are cooperating with Canadian scientist John Dick: each country paying its own way. Stanford's team is led by Irv Weissman, and includes Ravindra Majeti, Branimir Sikic and Bruno Medeiros, in cooperation with United Kingdom scientists Paresh Vyas and Denis Talbot, both of the University of Oxford.

What do the two teams have in common? A new way of looking at cancer:

"Some leukemia cells possess stem cell properties (which) promote leukemia growth. These (are) resistant to...treatment... Existing drugs (fail to) eliminate (the cells)...which persist in patients despite therapy, and continue to grow, spread, invade and kill..."

Stem cells, it seems, have an "evil twin": the Leukemia Stem Cell (LSC), or cancer stem cell, which does not die as readily from the chemo/radiation treatment. The LSC starts the leukemia, developing a bunch of bad cells. The chemo/radiation treatment may kill most of these secondary cells -- but not all of the LSCs, which go into hibernation for a while, and then come back.

That is the remission: when patients get better for a short time. Most of the leukemia is gone, but the cause of it remains, and waits, and then starts over again.

Think of LSCs as little monsters, with markers on their backs. These "surface markers" can be new targets for therapy. Other markers identify cancer cells as threats, giving out what are called "EAT ME" signals. The body's fighting cells (macrophages) kill and eat them. If the body can detect the LSCs, it will fight them.

Trouble is, the beast knows how to hide.

The LSCs can hide the surface marker under a little "cloak" (a protein coating known as CD47) on their backs. The cloak sends a stronger message, like "DON'T EAT ME!" Accordingly, the body's immune system does not recognize the LSCs as threats, and does not fight them.

The UCSD team has identified and named a marker on one of these leukemia stem cells, calling it ROR1 (roar-one). For the first time, the enemy has been clearly identified. There it is: the beast itself.

But it is not enough to recognize an enemy; it must also be fought, and in a way that does not destroy healthy cells.

Tom Kipps of the UCSD team invented what Dr. Jamieson describes as a "heat-seeking missile" to go after ROR1. This is an antibody, called UC961. That could be an acronym to remember, UC961 -- UC, like the University of California -- to the rescue!

Everything depends on defeating the "cloaking device", CD47, so it will not be able to shelter the cancer while it does its deadly work.

The other disease team is led by stem cell pioneer Irv Weissman, who has been working to defeat CD47 for more than a decade, since he found the "don't eat me" signal on mouse leukemia stem cells.

What is the difference between the two team's 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 that it can fight the blood cancer."

Think of that: if the cloaking device could be removed, the body's own defense system could attack the monster cells. The Stanford team has developed an antibody (HU5F9--"hug you") designed to hug onto the cloak and peel it back, so the microscopic monster can be fought.

From Dr. Weissman's official report:

"Cancer stem cells...produce a cell surface 'invisibility cloak' (CD47) a 'don't eat me' signal...(Our) antibody counters the cloak, allowing the patient's natural immune system...to eliminate the cancer stem cells."

Their antibody blocks the "don't eat me" sign. After that, it is hoped (and early success suggests) that the macrophages will recognize the LSC's as threats -- and take care of business.

Amazingly, this may be an advance to fight not only leukemia, but all forms of cancer.

Read the next sentence carefully; it is wonderful.

"We have now demonstrated that Hu5F9 is effective at inhibiting the growth of ... tumors, including (cancers of the) breast, bladder, colon, ovaries, ... brain ... head and neck... and multiple myelomas."

Weissman also said: "Without CIRM (the California stem cell program), this program would not have left the starting gate. It was turned down for funding by the National Cancer Institute...The treatment was discovered at Stanford, taken to the current stage mainly by CIRM funding..."

What comes next? Human clinical trials are planned for early 2014.

Is one of these approaches (or a combination of them both) the answer to cancer? We cannot say. No one can predict the path or pace of science.

But some things we can know.

Without dedicated scientists like these, cure will not happen.

Without serious and reliable funding -- cure cannot happen.

And that is why the California stem cell program exists: bringing money and minds together, to ease suffering and save lives.