CIRM-Funded Clinical Trials Targeting Cancers

Welcome to the Month of CIRM!

As we mentioned in last Thursday’s blog, during the month of October we’ll be looking back at what CIRM has done since the agency was created by the people of California back in 2004. To start things off, we’ll be focusing on CIRM-funded clinical trials this week. Supporting clinical trials through our funding and partnership is a critical cornerstone to achieving our mission: to accelerate stem cell treatments to patients with unmet medical needs.

Over the next four days, we will post infographics that summarize CIRM-funded trials focused on therapies for cancer, neurologic disorders, heart and metabolic disease, and blood disorders. Today, we review the nine CIRM-funded clinical trial projects that target cancer. The therapeutic strategies are as varied as the types of cancers the researchers are trying to eradicate. But the common element is developing cutting edge methods to outsmart the cancer cell’s ability to evade standard treatment.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

Advertisements

Protein that turns normal cells into cancer stem cells offers target to fight colon cancer

colon-cancer

Colon cancer: Photo courtesy WebMD

Colon cancer is a global killer. Each year more than one million people worldwide are diagnosed with it; more than half a million die from it. If diagnosed early enough the standard treatment involves surgery, chemotherapy, radiation or targeted drug therapy to destroy the tumors. In many cases this may work. But in some cases, while this approach helps put people in remission, eventually the cancer returns, spreads throughout the body, and ultimately proves fatal.

Now researchers may have identified a protein that causes normal cells to become cancerous, and turn into cancer stem cells (CSCs). This discovery could help provide a new target for anti-cancer therapies.

Cancer stem cells are devilishly tricky. While most cancer cells are killed by chemotherapy or other therapies, cancer stem cells are able to lie dormant and hide, then emerge later to grow and spread, causing the person to relapse and the cancer to return.

In a study published in Nature Research’s Scientific Reports, researchers at SU Health New Orleans School of Medicine and Stanley S. Scott Cancer Center identified a protein, called SATB2, that appears to act as an “on/off” switch for specific genes inside a cancer cell.

In normal, healthy colorectal tissue SATB2 is not active, but in colorectal cancer it is highly active, found in around 85 percent of tumors. So, working with mice, the researchers inserted extra copies of the SATB2 gene, which produced more SATB2 protein in normal colorectal tissue. They found that this produced profound changes in the cell, leading to uncontrolled cell growth. In effect it turned a normal cell into a cancer stem cell.

As the researchers state in their paper:

“These data suggest that SATB2 can transform normal colon epithelial cells to CSCs/progenitor-like cells which play significant roles in cancer initiation, promotion and metastasis.”

When the researchers took colorectal cancer cells and inhibited SATB2 they found that this not only suppressed the growth of the cancer and it’s ability to spread, it also prevented those cancer cells from becoming cancer stem cells.

In a news release about the study Dr. Rakesh Srivastava,  the senior author on the paper, said the findings are important:

“Since the SATB2 protein is highly expressed in the colorectal cell lines and tissues, it can be an attractive target for therapy, diagnosis and prognosis.”

Because SATB2 is found in other cancers too, such as breast cancer, these findings may hold significance for more than just colorectal cancer.

The next step is to repeat the study in mice that have been genetically modified to better reflect the way colon cancer shows up in people. The team hope this will not only confirm their findings, but also give them a deeper understanding of the role that SATB2 plays in cancer formation and spread.

New Cellular Tracking Device Tests Ability of Cell-Based Therapies to Reach Intended Destination

Therapies aimed at replacing damaged cells with a fresh, healthy batch hold immense promise—but there remains one major sticking point: once you have injected new, healthy cells into the patient, how do you track them and how do you ensure they do the job for which they were designed?

New tracking technique could improve researchers' ability to test potential cell therapies.

New tracking technique could improve researchers’ ability to test potential cell therapies.

Unfortunately, there’s no easy solution. The problem of tracking the movement of cells during cell therapy is that it’s hard to stay on their trail they enter the body. They can get mixed up with other, native cells, and in order to test whether the therapy is working, doctors often have to rely on taking tissue samples.

But now, scientists at the University of California, San Diego School of Medicine and the University of Pittsburgh have devised an ingenious way to keep tabs on where cells go post injection. Their findings, reported last week in the journal Magnetic Resonance in Medicine, stand to help researchers identify whether cells are arriving at the correct destination.

The research team, lead by UCSD Radiology Professor Dr. Eric Ahrens, developed something called a periflourocarbon (PFC) tracer in conjunction with MRI technology. Testing this new technology in patients receiving immune cell therapy for colorectal cancer, the team found that they were better able to track the movement of the cells than with traditional methods.

“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Ahrens in a news release. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

They tagged these cells with atoms of fluorine, a compound that normally occurs at extremely low levels. After tagging the immune cells, the researchers could then see where they went after being injected. Importantly, the team found that more than one-half of the implanted cells left the injection site and headed towards the colon. This finding marks the first time this process had been so readily visible.

Ahrens explained the technology’s potential implications:

“The imaging agent technology has been shown to be able to tag any cell type that is of interest. It is a platform imaging technology for a wide range of diseases and applications.”

A non-invasive cell tracking solution could serve as not only as an attractive alternative to the current method of tissue sampling, it could even help fast-track through regulatory hurdles new stem cell-based therapies. According to Ahrens:

“For example, new stem cell therapies can be slow to obtain regulatory approvals in part because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells…. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”

What are the ways scientists see stem cells in the body? Check out our Spotlight Video on Magnetic Particle Imaging.

Stem Cell Stories that Caught our Eye: “Let it Grow” Goes Viral, Stroke Pilot Study, The Bowels of Human Stem Cells, Tumor ‘Safety Lock.’

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

“Let it Grow” Goes Viral (and National!): Last week on The Stem Cellar we shared one of our favorite student videos from our annual Creativity Program. The video, a parody of the hit song from the movie Frozen, highlighted the outstanding creativity of a group of high school students from City of Hope in Los Angeles. And now, the song has made a splash nationwide—with coverage from ABC 7 Bay Area and even NBC New York!

Students from the City of Hope practice their routine for the group video

Students from the City of Hope practice their routine for the group video

Watch the full video on our YouTube page.

Stroke Pilot Study Shows Promise. Researchers at Imperial College London are currently testing whether stem cells extracted from a patient’s bone marrow can reverse the after effects of a stroke.

Reporting in this week’s Stem Cells Translational Medicine the team, lead by Dr. Soma Banjeree, describe their pilot study in which they collect a type of bone marrow stem cells called CD34+ cells. These cells can give rise to cells that make up the blood and the blood vessel lining. Earlier research suggested that treating stroke victims with these cells can improve recovery after a stroke—not because they replace the brain cells lost during a stroke, but because they release a chemical that triggers brain cells to grow. So the team decided to take the next step with a pilot study of five individuals.

As reported in a recent news release, this initial pilot study was only designed to test the safety of the procedure. But in a surprising twist, all patients in the study also showed significant improvement over a period of six months post-treatment. Even more astonishing, three of the patients (who had suffered one of the most severe forms of stroke) were living assistance-free. But since the first six months after injury is a time when many patients see improved function, these results need to be tested in a controlled trial where not all patients receive the cells

Immediate next steps include using advancing imaging techniques to more closely monitor what exactly happens in the brain after the patients are treated.

Want to learn more about using stem cells to treat stroke? Check out our Stroke Fact Sheet.

Deep in the Bowels of Stem Cell Behavior. Another research advance from UK scientists—this time at Queen Mary University of London researchers—announces important new insight into the behavior of adult stem cells that reside in the human gastro-intestinal tract (which includes the stomach and intestines). As described in a news release, this study, which examined the stem cells in the bowels of healthy individuals, as well as cells from early-stage tumors, points to key differences in their behaviors. The results, published this week in the journal Cell Reports, point to a potential link between stem cell behavior and the development of some forms of cancer.

By measuring the timing and frequency of mutations as they occur over time in aging stem cells, the research team, led by senior author Dr. Trevor Graham, found a key difference in stem cell behaviors between healthy individuals, and those with tumors.

In the healthy bowel, there is a relative stasis in the number of stem cells at any given time. But in cancer, that delicate balance—called a ‘stem cell niche’—appears to get thrown out of whack. There appears to be an increased number of cells, paired with more intense competition. And while these results are preliminary, they mark the first time this complex stem cell behavior has been studied in humans. According to Graham:

“Unearthing how stem cells behave within the human bowel is a big step forward for stem cell research. We now want to use the methods developed in this study to understand how stem cells behave inside bowel cancer, so we can increase our understanding of how bowel cancer grows. This will hopefully shed more light on how we can prevent bowel cancer—the fourth most common cancer in the UK.”

Finding the ‘Safety Lock’ Against Tumor Growth. It’s one of the greatest risks when transplanting stem cells: the possibility that the transplanted cells will grow out of control and form tumors.

But now, scientists from Keio University School of Medicine in Japan have devised an ingenious method that could negate this risk.

Reporting in the latest issue of Cell Transplantation and summarized in a news release, Dr. Masaya Nakamura and his team describe how they transplanted stem cells into the spinal columns of laboratory mice.

And here’s where they switched things up. During the transplantation itself, all mice were receiving immunosuppressant drugs. But then they halted the immunosuppressants in half the mice post-transplantation.

Withdrawing the drugs post-transplantation, according to the team’s findings, had the interesting effect of eliminating the tumor risk, as compared to the group who remained on the drugs. Confirmed with bioluminescent imaging that tracked the implanted cells in both sets of mice, these findings suggest that it in fact may be possible to finely tweak the body’s immune response after stem-cell transplantation.

Want to learn more about stem cells and tumor risk? Check out this recent video from CIRM Grantee Dr. Paul Knoepfler: Paul Knoepfler Talks About the Tendency of Embryonic Stem Cells to Form Tumors.

Immune System “Double Agent” Fuels Colon Cancer Stem Cells, New Study Finds

Researchers have discovered that a type of cell normally tasked with defending the body against foreign invaders actually spurs the development of colon cancer stem cells. This discovery, published in the journal Immunity, offers new insight into why some forms of cancer come back again and again—even in the face of aggressive treatment.

Led by University of Michigan Medical School’s Dr. Weiping Zou, the research team uncovered how a subset of the human immune system is actually working against itself—by turning run-of-the-mill colon cancer cells into the far more dangerous cancer stem cells.

Cancer stem cells are a subpopulation of cancer cells that can self-renew, and transform into the many types of cells that are found in a tumor. They are a relatively new concept and are not quite fully understood—or even accepted at all—by researchers. But as Zou explained in today’s news release, they may hold the key to controlling aggressive cancers:

“If you want to control cancer stem cells through new therapies, then you need to understand what controls the cancer stem cells.”

The human body’s defense mechanism—its immune system—is managed by several types of T cells. In some forms of cancer, such as colon cancer, the T cells’ job is to attack and destroy the tumor cells.

But in this study, Zou and his team found one type of T cell that was going rogue. The Th22 T cell, rather than working with other T cells to target the tumor for destruction, Th22 actually acts as a ‘tumor helper,’ keeping the cells alive and helping them replicate—causing the tumor to grow.

Upon closer examination, the researchers identified a specific molecule within the Th22 cell, called DOT1L, which was the underlying culprit. In tumor samples taken from patients, the team found that when the samples had higher levels of DOT1L the patients had a survival time. According to the research team, these results suggest first of all that DOT1L could be used as a marker for colon cancer progression.

And if DOT1L levels could be artificially manipulated, Zou and his team foresee a way to halt Th22’s effects on tumor cells—thereby curbing the cells’ rogue tendencies.

Want to learn more about cancer stem cells? Check out our Spotlight on Cancer Stem Cells from our video archive.

Anne Holden