Glioblastoma is an aggressive form of cancer that invades brain tissue, making it extremely difficult to treat. Current therapies involving radiation and chemotherapy are effective in destroying the bulk of brain cancer cells, but they are not able to reach the brain cancer stem cells, which have the ability to grow and multiply indefinitely. These cancer stem cells enable the glioblastoma to continuously grow even after treatment, which leads to recurring tumor formation.
Dr. Jeremy Rich and his team at UC San Diego examined glioblastomas further by obtaining glioblastoma tumor samples donated by patients that underwent surgery and implanting these into mice. Dr. Rich and his team tested a combinational treatment that included a targeted cancer therapy alongside a drug named teriflunomide, which is used to treatment patients with multiple sclerosis. The research team found that this approach successfully halted the growth of glioblastoma stem cells, shrank the tumor size, and improved survival in the mice.
In order to continue replicating, glioblastoma stem cells make pyrimidine, one of the compounds that make up DNA. Dr. Rich and his team noticed that higher rates of pyrimidine were associated with poor survival rates in glioblastoma patients. Teriflunomide works by blocking an enzyme that is necessary to make pyrmidine, therefore inhibiting glioblastoma stem cell replication.
In a press release, Dr. Rich talks about the potential these findings hold by stating that,
“We’re excited about these results, especially because we’re talking about a drug that’s already known to be safe in humans.”
However, he comments on the need to evaluate this approach further by saying that,
“This laboratory model isn’t perfect — yes it uses human patient samples, yet it still lacks the context a glioblastoma would have in the human body, such as interaction with the immune system, which we know plays an important role in determining tumor growth and survival. Before this drug could become available to patients with glioblastoma, human clinical trials would be necessary to support its safety and efficacy.”
The full results to this study were published in Science Translational Medicine.
There is nothing you can do to prevent or reduce your risk of leukemia. That’s not a very reassuring statement considering that this year alone almost 62,000 Americans will be diagnosed with leukemia; almost 23,000 will die from the disease. That’s why CIRM is funding four clinical trials targeting leukemia, hoping to develop new approaches to treat, and even cure it.
also why our next special Facebook Live “Ask the Stem Cell Team” event is
focused on this issue. Join us on Thursday, August 29th from
1pm to 2pm PDT to hear a discussion about the progress in, and promise of,
stem cell research for leukemia.
two great panelists joining us:
Dr. Crystal Mackall, has many titles including serving as the Founding Director of the Stanford Center for Cancer Cell Therapy. She is using an innovative approach called a Chimeric Antigen Receptor (CAR) T Cell Therapy. This works by isolating a patient’s own T cells (a type of immune cell) and then genetically engineering them to recognize a protein on the surface of cancer cells, triggering their destruction. This is now being tested in a clinical trial funded by CIRM.
Natasha Fooman. To describe Natasha as a patient advocate would not do justice to her experience and expertise in fighting blood cancer and advocating on behalf of those battling the disease. For her work she has twice been named “Woman of the Year” by the Leukemia and Lymphoma Society. In 2011 she was diagnosed with a form of lymphoma that was affecting her brain. Over the years, she would battle lymphoma three times and undergo chemotherapy, radiation and eventually a bone marrow transplant. Today she is cancer free and is a key part of a CIRM team fighting blood cancer.
We hope you’ll join
us to learn about the progress being made using stem cells to combat blood
cancers, the challenges ahead but also the promising signs that we are
advancing the field.
We also hope you’ll take an active role by posting questions on Facebook during the event, or sending us questions ahead of time to email@example.com. We will do our best to address as many as we can.
link to the event, feel free to share this with anyone you think might be interested
in joining us for Facebook Live “Ask the Stem Cell Team about Leukemia”
Getting a breast cancer diagnosis is devastating news in and of itself. Currently, there are treatment options that target three different types of receptors, which are named hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR), commonly found in breast cancer cells, . Unfortunately, in triple-negative breast cancer, which occurs in 10-20% of breast cancer cases, all three receptors are absent, making this form of breast cancer very aggressive and difficult to treat.
In recent years, researchers have discovered that proteins on the cell surface can tell macrophages, an immune cell designed to detect and engulf foreign or abnormal cells, not to eat and destroy them. This can be useful to help normal cells keep the immune system from attacking them, but cancer cells can also use these “don’t eat me” signals to hide from the immune system.
In fact, because of this concept, a CIRM-funded clinical trial is being conducted that uses an antibody called 5F9 to block a “don’t eat me” signal known as CD47 that is found in cancer cells. The results of this trial, which have been announced in a previous blog post, are very promising.
Further building on this concept, a CIRM-funded study has now discovered a potential new target for triple-negative breast cancer as well as ovarian cancer. Dr. Irv Weissman and a team of researchers at Stanford University have discovered an additional “don’t eat me” signal called CD24 that cancers seem to use to evade detection and destruction by the immune system.
In a press release, Dr. Weissman talks about his work with CD47 and states that,
“Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don’t eat me’ signals.”
The scientists began by looking for signals that were produced more highly in cancers than in the tissues from which the cancers arose. It is here that they discovered CD24 and then proceeded to implant human breast cancer cells in mice for testing. When the CD24 signaling was blocked, the mice’s immune system attacked the cancer cells.
An important discovery was that ovarian and triple-negative breast cancer were highly affected by blocking of CD24 signaling. The other interesting discovery was that the effectiveness of CD24 blockage seems to be complementary to CD47 blockage. In other words, some cancers, like blood cancers, seem to be highly susceptible to blocking CD47, but not to CD24 blockage. For other cancers, like ovarian cancer, the opposite is true. This could suggest that most cancers will be susceptible to the immune system by blocking the CD24 or CD47 signal, and that cancers may be even more vulnerable when more than one “don’t eat me” signal is blocked.
Dr. Weissman and his team are now hopeful that potential therapies to block CD24 signaling will follow in the footsteps of the clinical trials related to CD47.
Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $9.28 million to Dr. Saul Priceman at City of Hope to conduct a clinical trial for the treatment of breast cancer related brain metastases, which are tumors in the brain that have spread from the original site of the breast cancer.
This award brings the total number of CIRM-funded clinical trials to 56.
Breast cancer is the second-most common cancer in women, both in the United States (US) and worldwide. It is estimated that over 260,000 women in the US will be diagnosed with breast cancer in 2019 and 1 out of 8 women in the US will get breast cancer at some point during her lifetime. Some types of breast cancer have a high likelihood of metastasizing to the brain. When that happens, there are few treatment options, leading to a poor prognosis and poor quality of life.
Dr. Priceman’s clinical trial is testing a therapy to treat brain metastases that came from breast cancers expressing high levels of a protein called HER2. The therapy consists of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells. The T cells are modified with a protein called a chimeric antigen receptor (CAR) that recognizes the tumor protein HER2. These modified T cells (CAR-T cells) are then infused into the patient’s brain where they are expected to detect and destroy the HER2-expressing tumors in the brain.
CIRM has also funded the earlier work related to this study, which was critical in preparing the therapy for Food and Drug Administration (FDA) approval for permission to start a clinical trial in people.
“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news,” says Maria T. Millan, M.D., the President and CEO of CIRM. “There are few options for patients with breast cancer brain metastases. Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months. CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”
The CIRM Board also approved investing $19.7 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.
Dr. Mark Tuszynski at the University of California San Diego (UCSD) was awarded $6.23 million to develop a therapy for spinal cord injury (SCI). Dr. Tuszynski will use human embryonic stem cells (hESCs) to create neural stem cells (NSCs) which will then be grafted at the injury site. In preclinical studies, the NSCs have been shown to help create a kind of relay at the injury site, restoring communication between the brain and spinal cord and re-establishing muscle control and movement.
Dr. Mark Humayun at the University of Southern California (USC) was awarded $3.73 million to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD), the leading cause of vision loss in the US.
The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dry AMD, supporting the survival of photoreceptors in the affected retina, the kind of cells damaged by the disease.
The TRAN1 awards went to:
Stay tuned for our next blog which will dive into each of these awards in much more detail.
At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.
This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.
Talking research, unscrupulous clinics, and sustaining the momentum
In 2007, Jan Nolta
returned to Northern California from St. Louis to lead what was at the
time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program
and the Institute for Regenerative Cures, she has overseen the opening
of the institute, more than $140 million in research grants, and dozens
upon dozens of research studies. She recently sat down to answer some
questions about regenerative medicine and all the work taking place at UC Davis Health.
Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?
I am so excited about our research. We have about 20 different disease-focused teams.
That includes physicians, nurses, health care staff, researchers and
faculty members, all working to go from the laboratory bench to
patient’s bedside with therapies.
Perhaps the most promising and
exciting research right now comes from combining blood-forming
stem cells with gene therapy. We’re working in about
eight areas right now, and the first cure, something that we definitely
can call a stem cell “cure,” is coming from this combined approach.
doctors will be able to prescribe this type of stem cell therapy.
Patients will use their own bone marrow or umbilical cord stem cells.
Teams such as ours, working in good manufacturing practice
facilities, will make vectors, essentially “biological delivery
vehicles,” carrying a good copy of the broken gene. They will be
reinserted into a patient’s cells and then infused back into the
patient, much like a bone marrow transplant.
“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”
Along with treating the famous bubble baby disease,
where I had started my career, this approach looks very promising for
sickle cell anemia. We’re hoping to use it to treat several different
inherited metabolic diseases. These are conditions characterized by an
abnormal build-up of toxic materials in the body’s cells. They interfere
with organ and brain function. It’s caused by just a single enzyme.
Using the combined stem cell gene therapy, we can effectively put a good
copy of the gene for that enzyme back into a patient’s bone marrow stem
cells. Then we do a bone marrow transplantation and bring back a
person’s normal functioning cells.
The beauty of this therapy is
that it can work for the lifetime of a patient. All of the blood cells
circulating in a person’s system would be repaired. It’s the number one
stem cell cure happening right now. Plus, it’s a therapy that won’t be
rejected. These are a patient’s own stem cells. It is just one type of
stem cell, and the first that’s being commercialized to change cells
throughout the body.
Q: Let’s step back for a moment. In 2004, voters approved Proposition 71.
It has funded a majority of the stem cell research here at UC Davis and
throughout California. What’s been the impact of that ballot measure
and how is it benefiting patients?
We have learned so
much about different types of stem cells, and which stem cell will be
most appropriate to treat each type of disease. That’s huge. We had to
first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics.
We have one of them here at UC Davis and there are only five in the
entire state. These are clinics where the patients can go for
high-quality clinical stem cell trials approved by the FDA
[U.S. Food and Drug Administration]. They don’t need to go to
“unapproved clinics” and spend a lot of money. And they actually
“By the end of this year, we’ll have 50 clinical trials.”
By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.
Our Alpha Clinic
is right next to the hospital. It’s where we’ll be delivering a lot of
the immunotherapies, gene therapies and other treatments. In fact, I
might even get to personally deliver stem cells to the operating room
for a patient. It will be for a clinical trial involving people who have
broken their hip. It’s exciting because it feels full circle, from
working in the laboratory to bringing stem cells right to the patient’s
We have ongoing clinical trials
for critical limb ischemia, leukemia and, as I mentioned, sickle cell
disease. Our disease teams are conducting stem cell clinical trials
targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a
swallowing disorder], retinopathy [eye condition], Duchenne muscular
dystrophy and HIV. It’s all in the works here at UC Davis Health.
also great potential for therapies to help with renal disease and
kidney transplants. The latter is really exciting because it’s like a
mini bone marrow transplant. A kidney recipient would also get some
blood-forming stem cells from the kidney donor so that they can better
accept the organ and not reject it. It’s a type of stem cell therapy
that could help address the burden of being on a lifelong regime of
immunosuppressant drugs after transplantation.
Q: You and
your colleagues get calls from family members and patients all the
time. They frequently ask about stem cell “miracle” cures. What should
people know about unproven treatments and unregulated stem cell clinics?
That’s a great question.The number one rule is that if
you’re asked to pay money for a stem cell treatment, don’t do it. It’s a
big red flag.
When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”
there are unscrupulous people out there in “unapproved clinics” who
prey on desperate people. What they are delivering are probably not even
stem cells. They might inject you with your own fat cells, which
contain very few stem cells. Or they might use treatments that are not
matched to the patient and will be immediately rejected. That’s
dangerous. The FDA is shutting these unregulated clinics down one at a
time. But it’s like “whack-a-mole”: shut one down and another one pops
On the other hand, the Alpha Clinic is part of our
mission is to help the public get to the right therapy, treatment or
clinical trial. The big difference between those who make patients pay
huge sums of money for unregulated and unproven treatments and UC Davis
is that we’re actually using stem cells. We produce them in rigorously
regulated cleanroom facilities. They are certified to contain at least 99% stem cells.
and family members can always call us here. We can refer them to a
genuine and approved clinical trial. If you don’t get stem cells at the
beginning [of the clinical trial] because you’re part of the placebo
group, you can get them later. So it’s not risky. The placebo is just
saline. I know people are very, very desperate. But there are no miracle
cures…yet. Clinical trials, approved by the FDA, are the only way we’re
going to develop effective treatments and cures.
Scientific breakthroughs take a lot of patience and time. How do you and
your colleagues measure progress and stay motivated?
Motivation? “It’s all for the patients.”
all for the patients. There are not good therapies yet for many
disorders. But we’re developing them. Every day brings a triumph.
Measuring progress means treating a patient in a clinical trial, or
developing something in the laboratory, or getting FDA approval. The big
one will be getting biological license approval from the FDA, which
means a doctor can prescribe a stem cell or gene therapy treatment. Then
it can be covered by a patient’s health insurance.
I’m a cancer
survivor myself, and I’m also a heart patient. Our amazing team here at
UC Davis has kept me alive and in great health. So I understand it from
both sides. I understand the desperation of “Where do I go?” and “What
do I do right now?” questions. I also understand the science side of
things. Progress can feel very, very slow. But everything we do here at
the Institute for Regenerative Cures is done with patients in mind, and
We know that each day is so important when you’re watching
a loved one suffer. We attend patient events and are part of things
like Facebook groups, where people really pour their hearts out. We say
to ourselves, “Okay, we must work harder and faster.” That’s our
motivation: It’s all the patients and families that we’re going to help
who keep us working hard.
Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.
Bone metastasis –
where cancer starts in one part of the body, say the breast, but spreads to the
bones – is one of the most common complications of cancer. It can often result
in severe pain, increased risk of fractures and compression
of the spine. Tackling them is difficult because some cancer cells can
alter the environment around bone, accelerating the destruction of healthy bone
cells, and that in turn creates growth factors that stimulate the growth of the
cancer. It is a vicious cycle where one problem fuels the other.
Now researchers at
UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with
targeting agents. These act like a drug delivery device, offloading
different agents that simultaneously attack the cancer but protect the bone.
In a news release Weian Zhao, lead author of the study, said:
“What’s powerful about this
strategy is that we deliver a combination of both anti-tumor and anti-bone
resorption agents so we can effectively block the vicious circle between
cancers and their bone niche. This is a safe and almost nontoxic treatment
compared to chemotherapy, which often leaves patients with lifelong issues.”
published in the journal EBioMedicine,
has already been shown to be effective in mice. Next, they hope to be able to
do the safety tests to enable them to apply to the Food and Drug Administration
for permission to test it in people.
The team say if this
approach proves effective it might also be used to help treat other bone-related
diseases such as osteoporosis and multiple myeloma.
It’s never easy to tell someone that they are too late, that they missed the deadline. It’s particularly hard when you know that the person you are telling that to has spent years working on a project and now needs money to take it to the next level. But in science, as in life, it’s always better to tell people what they need to know rather than what they would like to hear.
And so, we have posted
a notice on our website for researchers thinking about applying for funding
that, except in a very few cases, they are too late, that there is no money
available for new projects, whether it’s Discovery, Translational or Clinical.
Here’s that notice:
that the budget allocation of funds for new awards under the CIRM clinical
program (CLIN1, CLIN2 and CLIN3) may be depleted within the next two to three
months. CIRM will accept applications for the monthly deadline on June 28, 2019
but will suspend application submissions after that date until further notice.
All applicants should note that the review of submitted applications may be
halted at any point in the process if funds are depleted prior to completion of
the 3-month review cycle. CIRM will notify applicants of such an occurrence.
Therefore, submission and acceptance of an application to CIRM does not
guarantee the availability of funds or completion of a review cycle.
of applications for the CIRM/NHLBI Cure Sickle Cell Initiative (CLIN1 SCD,
CLIN2 SCD) are unaffected and application submissions for this program will
We do, of course, have enough money set aside to continue
funding all the projects our Board has already approved, but we don’t have
money for new projects (except for some sickle cell disease projects).
In truth our funding has lasted a lot longer than anyone
anticipated. When Proposition 71 was approved the plan was to give CIRM $300
million a year for ten years. That was back in 2004. So what happened?
Well, in the early years stem cell science was still very
much in its infancy with most of the work being done at a basic or Discovery
level. Those typically don’t require very large sums so we were able to fund
many projects without hitting our $300m target. As the field progressed,
however, more and more projects were at the clinical trial stage and those need
multiple millions of dollars to be completed. So, the money went out faster.
To date we have funded 55 clinical trials and our
early support has helped more than a dozen other projects get into clinical
trials. This includes everything from cancer and stroke, to vision loss and
diabetes. It’s a good start, but we feel there is so much more to do.
Followers of news about CIRM know there is talk about a possible ballot initiative next year that would provide another $5.5 billion in funding for us to help complete the mission we have started.
Over the years we have built a pipeline of promising
projects and without continued support many of those projects face a difficult
future. Funding at the federal level is under threat and without CIRM there
will be a limited number of funding alternatives for them to turn to.
Telling researchers we don’t have any money to support their
work is hard. Telling patients we don’t have any money to support work that
could lead to new treatments for them, that’s hardest of all.
While we are here at ISSCR 2019 hearing various scientists talk about their work, we realize that there are various breakthroughs in stem cell research in a wide variety of different fields going on every day. It is wonderful to see how scientists are hard at work in developing the latest science and pushing innovation. Here are two remarkable stories you may have missed this week.
Scientists developing way to help premature babies breathe easier
Researchers at Cincinnati Children’s Hospital Medical Center are looking at ways to stimulate lung development in premature infants who suffer from a rare condition called Bronchopulmonary Dysplasia (BPD), which can cause lifelong breathing problems and even death. Using a mouse model of BPD, extensive analysis, and testing, the scientists were able to create a proposal to develop a stem cell therapy based on what are called c-KIT endothelial progenitor cells.
Premature babies, unable to breathe on their own, rely on machines to help them breathe. Unfortunately, these machines can interfere with lung development as well. The cells proposed in the stem cell therapy are common in the lungs of infants still in the womb and help in the formation of capillaries and air sacs in the lungs called alveoli.
In a press release, Dr. Vlad Kalinichenko, lead investigator for this work, was quoted as saying,
“The cells are highly sensitive to injury by high oxygen concentrations, so lung development in premature babies on mechanical oxygen assistance is impeded. Our findings suggest using c-KIT-positive endothelial cells from donors, or generating them with pluripotent stem cells, might be a way to treat BPD or other pediatric lung disorders associated with loss of alveoli and pulmonary microvasculature.”
The full results were published in American Journal of Respiratory and Critical Care Medicine.
Mice with a human immune system help research into cancer and infections
Speaking of a mouse model, researchers from Aarhus University and Aarhus University Hospital have succeeded in using mice with a transplanted human immune system to study functions in the immune system which are otherwise particularly difficult to study. This work could open the possibilities towards looking further into disease areas such as cancer, HIV, and autoimmune diseases.
Before potential treatments can be tested in humans, there needs to be extensive animal testing and data generated. However, when the disease relate’s to the human immune system, it can be particularly challenging to evaluate this in mice. The research team succeeded in transplanting human stem cells into mice whose own immune system is disabled, and then triggered a type of reaction in the immune system which normally reacts to meeting a range of viruses and bacteria.
In a press release, Dr. Anna Halling Folkmar, one of the researchers behind the study, says that,
“The humanised mice are an important tool in understanding how human immune cells behave during diseases and how they react to different medical treatments.”
I often joke that my
job here at CIRM is to be the official translator for the stem cell agency. I
have to translate complex science into everyday English that people without a
science background – that includes me – can understand.
Think I’m joking? Try making sense of this.
See what I mean. If
you are a scientist this is not only perfectly clear, it’s also quite exciting.
But for the rest of us……..
Actually, it is really quite exciting news. It’s about a CIRM-funded
clinical trial being run by Oncternal
Therapeutics to treat people with chronic lymphocytic leukemia (CLL), a
kind of cancer where our body makes too many white blood cells. The study is
using a combination therapy of Cirmtuzumab (a
monoclonal antibody named after us because we helped fund its development) and
ibrutinib, a conventional therapy used to treat cancers like CLL.
and then attaches itself to a protein on the surface of cancer stem cells that
the cancer needs to survive and spread. This attachment disables the protein
(called ROR1) which slows the growth of the leukemia and makes it more
vulnerable to anti-cancer drugs like ibrutinib.
In this Phase 1/2 clinical trial 12 patients were given the
combination therapy for 24 weeks or more, making them eligible to determine how
effective, or ineffective, the therapy is:
of the 12 patients had either a partial response – meaning a reduction in the amount
of detectable cancer – or a complete response to the treatment – meaning no
of the patients saw their cancer spread or grow
of the patients completed a year of treatment and they all showed signs of a
complete response including no enlarged lymph nodes and white blood cell counts
in the normal range.
combination therapy is also being used to treat people with Mantle Cell
Lymphoma (MCL), a rare but fast-growing form of blood cancer. The results from
this group, while preliminary, are also encouraging. One patient, who had
experienced a relapse following a bone marrow transplant, experienced a
complete response after three months of cirmtuzumab and ibrutinib.
data on the clinical trial was presented at a poster session (that’s the poster
at the top of this blog) at the annual meeting of the American Society of
In a news release Dr. James Breitmeyer, the President & CEO of Oncternal, said the results are very encouraging:
“These data presented today,
taken together with an earlier Phase 1 study of cirmtuzumab as a monotherapy in
relapsed/refractory CLL, give us increased confidence in the potential for
cirmtuzumab as a treatment for patients with ROR1-expressing lymphoid
malignancies, particularly in combination with ibrutinib as a potential
treatment for patients with CLL and MCL. We believe that the data also help to
validate the importance of ROR1 as a therapeutic target,”
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are both types of blood cancers that can be difficult to treat. CIRM is fundingForty Seven, Inc. to conduct a clinical trial to treat patients with these blood cancers with an antibody called 5F9. CIRM has also given multiple awards prior to the clinical trial to help in developing the antibody.
Cancer cells express a signal known as CD47, which sends a “don’t eat me” message to macrophages, which are white blood cells that are part of the immune system designed to “eat” and destroy unhealthy cells. The antibody works by blocking the signal, enabling the body’s own immune system to detect and destroy the cancer cells.
In a press release, Forty Seven, Inc. announced early clinical results from their CIRM funded trial using the antibody to treat patients with AML and MDS. Some patients received just the antibody while others received the antibody in combination with azacitidine, a chemotherapy drug used to treat these cancers.
Here is a synopsis of the trial:
35 patients treated in a Phase 1 clinical trial have been evaluated for a response assessment to-date.
10 of these have MDS or AML and only received the 5F9 antibody.
11 of these have higher-risk MDS and received the 5F9 antibody along with the chemotherapy drug azacitidine.
14 of these have untreated AML and received the 5F9 antibody along with the chemotherapy drug azacitidine.
For the 11 patients with higher-risk MDS treated with the antibody and chemotherapy, they found that:
All 11 patients achieved an objective response rate (ORR),meaning that there was a reduction in tumor burden of a predefined amount.
Six of these patients achieved a complete response (CR), indicatinga disappearance of all signs of cancer in response to treatment.
For the 14 patients with untreated AML treated with the antibody and chemotherapy, they found that:
Nine of these patients achieved an ORR.
Five of theseninepatients achieved a CR.
Two of these nine patientsachieved a morphologic leukemia-free state (MLFS), indicating the disappearance of all cells with formal and structural characteristics of leukemia, accompanied by bone marrow recovery, in response to treatment.
The remaining five patients achieved stable disease (SD), meaning that the tumor is neither growing nor shrinking.
The results also showed that:
There was no evidence of increased toxicities when the antibody was used alongside the chemotherapy drugs, demonstrating tolerance and safety of the treatment.
No responding MDS or AML patient has relapsed or progressed on the antibody in combination with chemotherapy, with a median follow-up of 3.8 months.
The median time to response was rapid at 1.9 months.
Several patients have experienced deepening responses over time resulting in complete remissions.
Based on the favorable results observed in this clinical trial to-date, expansion cohorts have been initiated, meaning that additional patients will be enrolled in a phase I trial. This will include patients with both higher-risk MDS and untreated AML as well as using the antibody in combination with chemotherapy.
In the press release, Dr. David Sallman, an investigator in the clinical trial, is quoted as saying,
“These new data for 5F9 show encouraging clinical activity in a broad population of patients with MDS and AML, who may be unfit for existing therapeutic options or at higher-risk for developing rapidly-advancing disease. Despite an evolving treatment landscape, physicians continue to seek new therapies for MDS and AML that can be used safely in combination with standard-of-care to help patients more rapidly achieve durable responses. To that end, I am excited to see meaningful clinical activity in a majority of patients treated with 5F9 in combination with azacitidine, with a median time to response of under two months and no relapses or progressions among responding patients.”