A cancer therapy developed at a CIRM Alpha Stem Cell Clinic tests its legs against breast cancer

Breast cancer cells

Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein on the cell surface membrane stained green. Image courtesy The National Institutes of Health

A Phase 1 clinical trial co-sponsored by CIRM and Oncternal Therapeutics, has started treating patients at UC San Diego (UCSD). The goal of the trial is to test the safety and anti-tumor activity of the Oncternal-developed drug, cirmtuzumab, in treating breast cancer.

Breast cancer is the second most common cancer to occur in women, regardless of race or ethnicity. More than 260,000 new cases are expected to be diagnosed this year in the United States alone. Typically, breast cancer cases are treated by a combination of surgery to remove the tumor locally, followed by some kind of systemic treatment, like chemotherapy, which can eliminate cancer cells in other parts of the body. In certain cases, however, surgery might not be a feasible option. Cirmtuzumab may be a viable option for these patients.

The drug acts by binding to a protein called ROR1, which is highly abundant on the surface of cancer cells. By blocking the protein Cirmtuzumab is able to promote cell death, stopping the cancer from spreading around the body.

Because ROR1 is also found on the surface of healthy cells there were concerns using cirmtuzumab could lead to damage to healthy tissue. However, a previous study revealed that using this kind of approach, at least in a healthy non-human primate model did not lead to any adverse clinical symptoms. Therefore, this protein is a viable target for cancer treatment and is particularly promising because it is a marker of many different types of cancers including leukemia, lung cancer and breast cancer.

Phase 1 clinical trials generally enroll a small number of patients who have do not have other treatment options. The primary goals are to determine if this approach is safe, if it causes any serious side-effects, what is the best dosage of the drug and how the drug works in the body. This clinical trial will enroll up to 15 patients who will receive cirmtuzumab in combination with paclitaxel (Taxol), a vetted chemotherapy drug, for six months.

Earlier this year, a similar clinical trial at UCSD began to test the effectiveness a of cirmtuzumab-based combination therapy to treat patients with B-cell cancers such as chronic lymphocytic leukemia. This trial was also partially funded by CIRM.

In a press release, Dr. Barbara Parker, the co-lead on this study states:

“Our primary objective, of course, is to determine whether the drug combination is safe and tolerable and to measure its anti-tumor activity. If it proves safe and shows effectiveness against breast cancer, we can progress to subsequent trials to determine how best to use the drug combination.”

CIRM-funded clinical trial takes a combination approach to treating deadly blood cancers

Stained blood smear shows enlarged chronic lymphocytic leukemia cells among normal red blood cells. (UCSD Health)

A diagnosis of cancer often means a tough road ahead, with surgery, chemotherapy and radiation used to try and kill the tumor. Even then, sometimes cancer cells manage to survive and return later, spreading throughout the body. Now researchers at UC San Diego and Oncternal Therapeutics are teaming up with a combination approach they hope will destroy hard-to-kill blood cancers like leukemia.

The combination uses a monoclonal antibody called cirmtuzumab (so called because CIRM funding helped develop it) and a more traditional anti-cancer therapy called ibrutinib. Here’s how it is hoped this approach will work.

Ibrutinib is already approved by the US Food and Drug Administration (FDA) to treat blood cancers such as leukemia and lymphoma. But while it can help, it doesn’t always completely eradicate all the cancer cells. Some cancer stem cells are able to lie dormant during treatment and then start proliferating and spreading the cancer later. That’s why the team are pairing ibrutinib with cirmtuzumab.

In a news release announcing the start of the trial, UCSD’s Dr. Thomas Kipps,  said they hope this one-two punch combination will be more effective.

Thomas Kipps, UCSD

“As a result {of the failure to kill all the cancer cells}, patients typically need to take ibrutinib indefinitely, or until they develop intolerance or resistance to this drug. Cirmtuzumab targets leukemia and cancer stem cells, which are like the seeds of cancer. They are hard to find and difficult to destroy. By blocking signaling pathways that promote neoplastic-cell growth and survival, cirmtuzumab may have complementary activity with ibrutinib in killing leukemia cells, allowing patients potentially to achieve complete remissions that permit patients to stop therapy altogether.”

Because this is an early stage clinical trial, the goal is to first make sure the approach is safe, and second to identify the best dose and treatment schedule for patients.

The researchers hope to recruit 117 patients around the US. Some will get the cirmtuzumab and ibrutinib combination, some will get ibrutinib alone to see if one approach is more effective than the other.

CIRM has a triple investment in this research. Not only did our funding help develop cirmtuzumab, but CIRM is also funding this clinical trial and one of the trial sites is at UCSD, one of the CIRM Alpha Stem Cell Clinics.

CIRM’s Dr. Ingrid Caras says this highlights our commitment to our mission of accelerating stem cell therapies to patients with unmet medical needs.

“Our partnership with UC San Diego and the Alpha Stem Cell Clinics has enabled this trial to more quickly engage potential patient-participants. Being among the first to try new therapies requires courage and CIRM is grateful to the patients who are volunteering to be part of this clinical trial.”


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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.