CIRM-supported study shows promise in fighting acute myeloid leukemia

Chemotherapy

Chemotherapy

For years chemotherapy has been a mainstay in the war against cancer. While it can be very effective it can also come with some nasty side effects. Since chemo works by killing rapidly growing cells, it not only hits the cancer cells, but can also hit other rapidly growing cells too, including those in our hair roots, which is why many people undergoing chemo lose their hair.

So, the key to a truly effective anti-cancer therapy is one that does as much damage as possible to the cancer cells, and as little as possible to all the healthy cells in the body. A therapy being developed by Cellerant Therapeutics seems to have found that sweet spot in a new therapy targeting acute myeloid leukemia (AML).

AML starts in the bone marrow and quickly moves into the blood, where it can spread to other parts of the body. It is the second most common form of leukemia and claims around 10,000 lives in the US every year. Chemotherapy is the main weapon used against AML but it can also cause nausea, hair loss and other complications and in most cases has limited effectiveness because, over time, the leukemia cells get used to it.

Cellerant 2013In a study published in the journal Blood Advances, Cellerant researchers explain the limitations of existing treatments.

“The current standard of care for acute myeloid leukemia (AML) is largely ineffective with very high relapse rates and low survival rates, mostly due to the inability to eliminate a rare population of leukemic stem cells (LSCs) that initiate tumor growth and are resistant to standard chemotherapy.”

Cellerant has developed a therapy called CLT030 which targets CLL1, a marker found on the surface of leukemia cells but not on normal blood stem cells. Preclinical studies in mice show CLT030 is able to zero in on this surface marker and attack the leukemia but do little damage to blood or other surrounding cells.

In a news release, Ram Mandalam, President and CEO of Cellerant, said this is encouraging news:

“AML remains a significant unmet medical need, and our therapy, CLT030, that can target leukemic stem cells precisely while minimally affecting normal hematopoietic stem cells could improve outcomes while avoiding much of the toxicities associated with conventional chemotherapy and other targeted therapeutics.”

Mandalam says they are now doing the late-stage preclinical testing to be able to apply to the Food and Drug Administration for permission to start a clinical trial. CIRM is funding this stage of the research.

 

Seeing is believing. Proof a CIRM-funded therapy is making a difference

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Thelma, participant in the CAMELLIA clinical trial

You have almost certainly never heard of Thelma, or met her, or know anything about her. She’s a lady living in England who, if it wasn’t for a CIRM-funded therapy, might not be living at all. She’s proof that what we do, is helping people.

Thelma is featured in a video about a treatment for acute myeloid leukemia, one of the most severe forms of blood cancer. Thelma took part in a clinical trial, called CAMELLIA, at Oxford Cancer Centre in Oxford, UK. The clinical trial uses a therapy that blocks a protein called CD47 that is found on the surface of cancer cells, including cancer stem cells which can evade traditional therapies. The video was shot to thank the charity Bloodwise for raising the funds to pay for the trial.

Prof. Paresh Vyas of Oxford University, who was part of the clinical trial team that treated Thelma, says patients with this condition face long odds.

“Patients with acute myeloid leukemia have the most aggressive blood cancer. We really haven’t had good treatments for this condition for the last 40 years.”

While this video was shot in England, featuring English nurses and doctors and patients, the therapy itself was developed here in California, first at Stanford University under the guidance of Irv Weissman and, more recently, at Forty Seven Inc. That company is now about to test their approach in a CIRM-funded clinical trial here in the US.

This is an example of how CIRM doesn’t just fund research, we invest in it. We help support it at every stage, from the earliest research through to clinical trials. Without our early support this work may not have made it this far.

The Forty Seven Inc. therapy uses the patient’s own immune system to help fight back against cancer stem cells. It’s looking very promising. But you don’t have to take our word for it. Take Thelma’s.

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.

Stories that caught our eye: new target for killing leukemia cancer stem cells and stem cell vesicles halt glaucoma

New stem cell target for acute myeloid leukemia (Karen Ring).  A new treatment for acute myeloid leukemia, a type of blood cancer that turns bone marrow stem cells cancerous, could be in the works in the form of a cancer stem cell destroying antibody.

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Acute Myeloid Leukemia (Credit: Medscape)

Scientists from the NYU Langone Medical Center and the Memorial Sloan Kettering Cancer Center identified a protein called CD99 that appears more abundantly on the surface of abnormal blood cancer stem cells compared to healthy blood stem cells. They developed an antibody that specifically recognizes and kills the CD99 wielding cancer stem cells while leaving the healthy blood stem cells unharmed.

The CD99 antibody was effective at killing human AML stem cells in a dish and in mice that were transplanted with the same type of cancer stem cells. Further studies revealed that the CD99 antibody when attached to the surface of cancer stem cells, sets off a cascade of enzyme activity that causes these cells to die. These findings suggest that cancer stem cells express more CD99 as a protective mechanism against cell death.

In an interview with Genetic Engineering and Biotechnology News, Chris Park, senior author on the Science Translational Medicine study, explained the importance of their work:

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we also show that antibodies against this target can directly kill human AML stem cells. While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

While this work is still in the early stages, Dr. Park stressed that his team is actively working to translate their CD99 antibody therapy into clinical trials.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials.”

 

Peculiar stem cell function may help treat blindness (Todd Dubnicoff). Scientists at the National Eye Institute (NEI) have uncovered a novel function that stem cells use to carry out their healing powers and it may lead to therapies for glaucoma, the leading cause of blindness in United States. Reporting this week in Stem Cells Translational Medicine, the researchers show that stem cells send out regenerative signals by shedding tiny vesicles called exosomes. Once thought to be merely a garbage disposal system, exosomes are now recognized as an important means of communication between cells. As they bud off from the cells, the exosomes carry proteins and genetic material that can be absorbed by other cells.

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

The researchers at NEI isolated exosomes from bone marrow stem cells and injected them into the eyes of rats with glaucoma symptoms. Without treatment, these animals lose about 90 percent of their retinal ganglion cells, the cells responsible for forming the optic nerve and for sending visual information to the brain. With the exosome treatment, the rats only lost a third of the retinal ganglion cells. The team determined that microRNAs – small genetic molecules that can inhibit gene activity – inside the exosome were responsible for the effect.

Exosomes have some big advantages over stem cells when comes to developing and manufacturing therapies which lead author Ben Mead explains in a press release picked up by Eureka Alert:

“Exosomes can be purified, stored and precisely dosed in ways that stem cells cannot.”

We’ll definitely keep our eyes on this development. If these glaucoma studies continue to look promising it stands to reason that there would be exosome applications in many other diseases.