Newly developed biosensor can target leukemic stem cells

Dr. Michael Milyavsky (left) and his research student Muhammad Yassin (right). Image courtesy of Tel Aviv University.

Every three minutes, one person in the United States is diagnosed with a blood cancer, which amounts to over 175,000 people every year. Every nine minutes, one person in the United States dies from a blood cancer, which is over 58,000 people every year. These eye opening statistics from the Leukemia & Lymphoma Society demonstrate why almost one in ten cancer deaths in 2018 were blood cancer related.

For those unfamiliar with the term, a blood cancer is any type of cancer that begins in blood forming tissue, such as those found in the bone marrow. One example of a blood cancer is leukemia, which results in the production of abnormal blood cells. Chemotherapy and radiation are used to wipe out these cells, but the blood cancer can sometimes return, something known as a relapse.

What enables the return of a blood cancer such as leukemia ? The answer lies in the properties of cancer stem cells, which have the ability to multiply and proliferate and can resist the effects of certain types of chemotherapy and radiation. Researchers at Tel Aviv University are looking to decrease the rate of relapse in blood cancer by targeting a specific type of cancer stem cell known as a leukemic stem cell, which are often found to be the most malignant.

Dr. Michael Milyavsky and his team at Tel Aviv University have developed a biosensor that is able to isolate, label, and target specific genes found in luekemic stem cells. Their findings were published on January 31, 2019 in Leukemia.

In a press release Dr. Milyavsky said:

“The major reason for the dismal survival rate in blood cancers is the inherent resistance of leukemic stem cells to therapy, but only a minor fraction of leukemic cells have high regenerative potential, and it is this regeneration that results in disease relapse. A lack of tools to specifically isolate leukemic stem cells has precluded the comprehensive study and specific targeting of these stem cells until now.”

In addition to isolating and labeling leukemic stem cells, Dr. Milyavsky and his team were able to demonstrate that the leukemic stem cells labeled by their biosensor were sensitive to an inexpensive cancer drug, highlighting the potential this technology has in creating more patient-specific treatment options.

In the article, Dr. Milyavsky said:

” Using this sensor, we can perform personalized medicine oriented to drug screens by barcoding a patient’s own leukemia cells to find the best combination of drugs that will be able to target both leukemia in bulk as well as leukemia stem cells inside it.”

The researchers are now investigating genes that are active in leukemic stem cells in the hope finding other druggable targets.

CIRM has funded two clinical trials that also use a more targeted approach for cancer treatment. One of these trials uses an antibody to treat chronic lymphocytic leukemia (CLL) and the other trial uses a different antibody to treat acute myeloid leukemia (AML).

Confusing cancer to kill it

Kipps

Thomas Kipps, MD, PhD: Photo courtesy UC San Diego

Confusion is not a state of mind that we usually seek out. Being bewildered is bad enough when it happens naturally, so why would anyone actively pursue it? But now some researchers are doing just that, using confusion to not just block a deadly blood cancer, but to kill it.

Today the CIRM Board approved an investment of $18.29 million to Dr. Thomas Kipps and his team at UC San Diego to use a one-two combination approach that we hope will kill Chronic Lymphocytic Leukemia (CLL).

This approach combines two therapies, cirmtuzumab (a monoclonal antibody developed with CIRM funding, hence the name) and Ibrutinib, a drug that has already been approved by the US Food and Drug Administration (FDA) for patients with CLL.

As Dr. Maria Millan, our interim President and CEO, said in a news release, the need for a new treatment is great.

“Every year around 20,000 Americans are diagnosed with CLL. For those who have run out of treatment options, the only alternative is a bone marrow transplant. Since CLL afflicts individuals in their 70’s who often have additional medical problems, bone marrow transplantation carries a higher risk of life threatening complications. The combination approach of  cirmtuzumab and Ibrutinib seeks to offer a less invasive and more effective alternative for these patients.”

Ibrutinib blocks signaling pathways that leukemia cells need to survive. Disrupting these pathways confuses the leukemia cell, leading to its death. But even with this approach there are cancer stem cells that are able to evade Ibrutinib. These lie dormant during the therapy but come to life later, creating more leukemia cells and causing the cancer to spread and the patient to relapse. That’s where cirmtuzumab comes in. It works by blocking a protein on the surface of the cancer stem cells that the cancer needs to spread.

It’s hoped this one-two punch combination will kill all the cancer cells, increasing the number of patients who go into complete remission and improve their long-term cancer control.

In an interview with OncLive, a website focused on cancer professionals, Tom Kipps said Ibrutinib has another advantage for patients:

“The patients are responding well to treatment. It doesn’t seem like you have to worry about stopping therapy, because you’re not accumulating a lot of toxicity as you would with chemotherapy. If you administered chemotherapy on and on for months and months and years and years, chances are the patient wouldn’t tolerate that very well.”

The CIRM Board also approved $5 million for Angiocrine Bioscience Inc. to carry out a Phase 1 clinical trial testing a new way of using cord blood to help people battling deadly blood disorders.

The standard approach for this kind of problem is a bone marrow transplant from a matched donor, usually a family member. But many patients don’t have a potential donor and so they often have to rely on a cord blood transplant as an alternative, to help rebuild and repair their blood and immune systems. However, too often a single cord blood donation does not have enough cells to treat an adult patient.

Angiocrine has developed a product that could help get around that problem. AB-110 is made up of cord blood-derived hematopoietic stem cells (these give rise to all the other types of blood cell) and genetically engineered endothelial cells – the kind of cell that lines the insides of blood vessels.

This combination enables the researchers to take cord blood cells and greatly expand them in number. Expanding the number of cells could also expand the number of patients who could get these potentially life-saving cord blood transplants.

These two new projects now bring the number of clinical trials funded by CIRM to 35. You can read about the other 33 here.