California’s Stem Cell Agency Accelerates Treatments to Patients

The following article is an Op Ed that appeared in today’s print version of the San Francisco Chronicle

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Biotechnology was born in California in the 1970s based on the discovery out of one of its universities and California is responsible for an industry that has impacted the lives of billions of people worldwide. In 2004, the voters of California approved Proposition 71, creating the California Institute for Regenerative Medicine and setting the state on the path to becoming a global leader in stem cell research. Today the therapies resulting from the institute’s work are not just changing lives, they are already saving lives.

Lives like Evie Vaccaro, who is alive today because of a treatment CIRM is funding. Vaccaro was born with SCID, also known as “bubble baby disease,” an immune disorder that often kills babies in their first two years. Vaccaro and dozens of other babies were given stem cell treatments thanks to the institute. All are showing improvement; some are now several years past treatment and considered cured.

An accident left Jake Javier from Danville paralyzed from the chest down on the eve of his high school graduation. Javier was treated in a CIRM-funded clinical trial. Today he has regained the use of his arms and hands, is driving a car and is a sophomore at Cal Poly San Luis Obispo. Five other patients treated at the same time as Javier have all experienced improvements meaning that instead of needing round-the-clock care, they can lead independent lives.

A study by the Tufts Center for the Study of Drug Development estimated it takes at least 10 years and $2.6 billion to develop one successful drug. In 14 years, and with just $3 billion, CIRM has funded 1,000 different projects, enrolled 900 patients, and supported 49 different clinical trials targeting diseases such as cancer, kidney failure and leukemia. Four of these programs have received an expedited designation by the U.S. Food and Drug Administration, meaning they could get faster approval to help more patients

We have created a network of world class medical clinics that have expertise in delivering treatments to patients. The CIRM Alpha Clinics offer treatments based on solid science, unlike the unlicensed clinics sprouting up around California that peddle unproven and potentially harmful therapies that cost patients thousands of dollars.

CIRM has:

  • Supported the creation of 12 stem-cell research facilities in California
  • Attracted hundreds of top-tier researchers to California
  • Trained a new generation of stem-cell scientists
  • Brought clinical trials to California — for example, one targeting ALS or Lou Gehrig’s disease
  • Deployed rigorous scientific standards and support so our programs have a “seal of approval” to attract $2.7 billion in additional investments from industry and other sources.

We recently have partnered with the National Institutes of Health to break down barriers and speed up the approval process to bring curative treatments to patients with Sickle Cell Disease.

Have we achieved all we wanted to? Of course not. The first decade of CIRM’s life was laying the groundwork, developing the knowledge and expertise and refining processes so that we can truly accelerate progress. As a leader in this burgeoning field of regenerative medicine, CIRM needs to continue its mission of accelerating stem-cell treatments to patients with unmet medical needs.

Dr. Maria T. Millan is President and CEO and Jonathan Thomas, JD, PhD, is the Board Chairman of the California Institute of Regenerative Medicine. 

 

 

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

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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.”

Stem Cell Stories that Caught Our Eye: Killer Cells May Treat Cancer, CIRM-Funded Trial Shows Promise and Worms to the Rescue – New Research Could Lead to Human Therapies

Stem cell image of the week:  Our stem cell image of the week shows natural killer cells (yellow) attacking a cancer cell (red).

The cancer fighters known as CAR T cells have proved their prowess in recent years. Three therapies using the altered T cells against lymphoma or leukemia have won U.S. Food and Drug Administration approval, and hundreds of trials are now unleashing them on other malignancies, including solid tumors. But the cells may soon have company. Researchers have equipped other immune guardians—natural killer cells and macrophages—with the same type of cancer-homing receptor, and the natural killer cells have made their debut in clinical trials.

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CAR T cells—their name comes from the chimeric antigen receptor, or CAR, added to help the immune cells target cancer cells—inspired the new work. CAR natural killer (CAR NK) cells could be safer, faster to produce, and cheaper, and they may work in situations where T cells falter. CAR-carrying macrophages also have potential advantages, and one firm plans to launch the first clinical trials of these cells next year.

Although they aren’t likely to replace CAR T cells, these alternative cancer fighters “could be an addition to the armamentarium of cell therapies,” says hematologist and oncologist Katy Rezvani of the University of Texas MD Anderson Cancer Center in Houston. She is leading the first trial of CAR NK cells in the United States, which began in 2017, and organizing another that is due to start this year.

“Natural killer cells are our first line of defense against cancer cells,” Rezvani says. They scan other cells in the body and destroy any that are infected or otherwise abnormal, including tumor cells. Researchers have been trying to harness the cancer-fighting activity of NK cells that don’t carry CARs for more than 20 years, notes translational immunologist Jeffrey Miller of the University of Minnesota in Minneapolis. But upgrading them by adding CARs seems to boost their potency.

CIRM-funded spinal cord injury trial produces more encouraging results (Kevin McCormack)

Way back in 2010 Geron became the first ever company to get approval from the Food and Drug Administration (FDA) to carry out a clinical trial using embryonic stem cells to treat people with spinal cord injury. CIRM funded that work and even though the company later halted the trial (for business reasons) it was a small piece of stem cell history.

Fast forward eight years and Asterias Biotherapeutics has taken up where Geron left off, using the same approach. This week Asterias published the latest results from its CIRM-funded clinical trial and they are encouraging.

They have done 24-month follow-ups on six patients (including Jake Javier and Chris Boesen who we have blogged about) who received 10 million cells transplanted into their spine. None experienced any serious side effects and MRI examinations showed evidence that the stem cells had engrafted at the injury site in all six patients. Often after a spinal cord injury a cavity can form at the injury site and scar tissue or fill up with fluid, preventing the spinal cord from healing. The evidence of engraftment means there is no such cavity.

Even more encouragingly all six have recovered at least one motor level (a measure of how much movement or function they have regained) on at least one side and five have recovered two or more motor levels on at least one side.

This kind of recovery can make the difference between needing round-the-clock care and being able to lead an independent life.

In a news release, Ed Wirth, the Chief Medical Officer at Asterias, said this shows the benefits of the therapy appear to be long-lasting:

“While the primary endpoint for the SCiStar trial was 12 months, we are further encouraged by this additional follow-up data that shows both durable engraftment and motor function recovery being maintained or improved upon at 24 months.”

The company hopes to meet with the FDA later this year to plan for a future trial of the therapy.

Planaria Worm Their Way into Human Stem Cell-Related Research (Todd Dubnicoff)

The planaria flatworm has astounding regenerative capabilities. Cut it in half and the missing side grows back. Decapitate it and the head grows back in about two weeks. Many researchers are eager to unlock the cellular and molecular mechanisms of planaria’s seemingly supernatural powers in order to bestow them onto humans suffering from disease or injury. But humans and worms are so different, how could you ever make any meaningful connections between the species?

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Decapitated planaria regrows head within a couple of weeks.                                 Photo credit: Michael Levin And Tal Shomrat, Tufts University

Well, in a report published this week, Oxford University researchers found that planaria have more in common with humans than was previously thought when it comes to the way both species regulate gene activity in stem cells. These findings make these worms an even more valid model system for exploring novel therapeutic strategies for people.

Up until this study, it was thought that only vertebrates (animals with back bones like mammals, birds and fish) use a mechanism called bivalency in their stem cells to maintain the ability to specialize into different types of cells. With bivalency, a subset of genes within stem cells are neither turned off nor turned on. Instead they’re in a “poised” state, ready to be silenced or activated depending on the eventual fate of that particular cell.

By studying the chemical modifications of DNA, called epigenetics, that play a role in gene activity and bivalency, the research team showed that bivalency is also employed by planaria, a simple invertebrate. Professor Aziz Aboobaker, the lead author on the study, explained the significance of this finding in a press release:

“The results of this approach served to confirm the team’s findings that bivalency seems likely to have evolved earlier in multicellular animal evolution than we thought, and this adds to the growing narrative that simple worm stem cells and our stem cells have much more in common then we imagined when we started this work.”

This commonality makes the easy-to-study planaria an attractive model system to study given that dysfunctions in these chemical modifications of DNA have been linked to human disease.

The study is published in Genome Research.

Deep dive into muscle repair yields new strategies to combat Duchenne muscular dystrophy

Researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) reported new findings this week that may lead to novel therapeutic strategies for people suffering from Duchenne muscular dystrophy (DMD). DMD, a muscle-wasting disease that affects 1 in 7250 males aged 5 to 24 years in the United States, is caused by a genetic mutation leading to the lack of a protein called dystrophin. Without dystrophin, muscle cells become fragile and are easily damaged. Instead of self-repair, the muscles are replaced by scar tissue, a process called fibrosis that leads to muscle degeneration and wasting.

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Dystrophin, a protein that maintains the structural integrity of muscle fibers, is missing in people with DMD. Image credit: Khan Academy

Boys with DMD first show signs of muscle weakness between ages 3-5 and often stop walking by the time they’re teenagers. Eventually the muscles critical for breathing and heart function stop working. Average life expectancy is 26 and there is no cure.

The SBP scientists are aiming to treat DMD by boosting muscle repair in affected individuals. But to do that, they sought to better understand how muscle regeneration works in the first place. In the current study, they focused their efforts on so-called fibro/adipogenic precursor (FAP) cells which, in response to acute injury, appear to play a role in stimulating muscle stem cells to divide and replace damaged muscle in healthy individuals. But FAPs are also implicated in the muscle wasting and scarring that’s seen in DMD.

By examining the gene activity of single FAP cells from mouse models of acute injury and DMD, the researchers identified a sub-population of FAP cells (sub-FAPs). Further study of these sub-FAPs showed that during early stages of muscle regeneration, these cells promote muscle stem cell activation but then at later stages, sub-FAPs – identified by a cell surface protein called Vcam1 – stimulate fibrosis. It turns out that during healthy acute muscle injury, the sub-FAPs with cell-surface Vcam1 protein are readily eaten up and removed by immune cells thereby avoiding muscle fibrosis. But in the DMD mouse model, removal of these sub-FAPs is impaired and instead collagen deposits and muscle fibrosis occur which are hallmarks of the progressive degeneration seen in DMD.

Barbora Malecova, Ph.D., a first author of the study, explained the implications of these results in a press release:

“This study elucidates the cellular and molecular pathogenesis of muscular dystrophy. These results indicate that removing or modulating the activity of Vcam1-positive sub-FAPs, which promote fibrosis, could be an effective treatment for DMD.”

The lab, led by Pier Lorenzo Puri, M.D., next will explore the possibility of finding drugs that target the Vcam1 sub-FAPs which in turn could help prevent fibrosis in DMD.

The study, funded in part by CIRM, appears in Nature Communications. CIRM is also funding a Phase 2 clinical trial testing a stem cell-based therapy that aims to improve the life-threatening heart muscle degeneration that occurs in DMD patients.

Regrowing dental tissue with stem cells from baby teeth

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Stem cells extracted from baby teeth were able to regenerate dental pulp (shown, with fluorescent labeling) in young patients who had injured one of their adult teeth.                       Photo courtesy of University of Pennsylvania

Young children can be full of life.

For parents that bubbly energy can be fun to observe and enjoy, but in other instances when they trip and fall, or do something that causes trauma to their mouth – their teeth can take a hit. Unfortunately when that trauma affects an immature permanent tooth, it can also hinder blood supply and root development, resulting in what is essentially a “dead” tooth.

Until recently the only treatment option was apexification, a procedure which encourages root development but doesn’t always fix the lost tissue. In fact, it’s been known to cause abnormal root development.

So what is a parent to do?

Turn to a clinical trial.

New results of a clinical trial, jointly led by Songtao Shi of the University of Pennsylvania, who has also previously received funding from CIRM, and researchers at the the Fourth Military Medicine University in Xi’an, China, suggest that there is a more promising path for children with these types of injuries: using stem cells extracted from the patient’s baby teeth.

The work was published in the journal Science Translational Medicine.

“This treatment gives patients sensation back in their teeth. If you give them a warm or cold stimulation, they can feel it; they have living teeth again,” says Shi, professor and chair in the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine. “So far we have follow-up data for two, two and a half, even three years and have shown it’s a safe and effective therapy.”

The Phase I trial, conducted in China enrolled 40 children who had each injured one of their permanent incisors and still had baby teeth. Thirty were assigned to receive a treatment of human dental pulp stem cells (hDPSC) and 10 to the control treatment, apexification.

Those that received hDPSC treatment had tissue extracted from a healthy baby tooth. Upon follow-up, the researchers found that patients who received hDPSCs had more signs than the control group of healthy root development and thicker dentin, the hard part of a tooth beneath the enamel. Blood flow increased as well. A year following the procedure, only those who received hDPSCs had regained some sensation. Examining a variety of immune-system components, the team found no evidence of safety concerns.

As further support of the treatment’s effectiveness, the researchers had the opportunity to directly examine the tissue of a treated tooth when the patient re-injured it and had to have it extracted. They found that the implanted stem cells regenerated different components of dental pulp, including the cells that produce dentin, connective tissue, and blood vessels.

But this is just a first step. While using a patient’s own stem cells reduces the chances of immune rejection, it’s not possible in adult patients who have lost all of their baby teeth.

Shi and colleagues are beginning to test the use of allogenic stem cells, or cells donated from another person, to regenerate dental tissue in adults. They are also hoping to secure FDA approval to conduct clinical trials using hDPSCs in the United States.

Maria Millan Opens Up About the Current State of CIRM

In an article published to the SF Chronicle last week, reporter Erin Allday and Joaquin Palomino discussed CIRM, and how our work as an agency has paid off since our inception in 2004.

The article, which is a part of a four part series, explores the hope and reality of the revolutionary science of stem cell therapy. It focuses on what has transpired since 2004, when California voters approved a $3 billion bond measure to fund stem cell research with the promise that it soon would produce new treatments for incurable diseases.

In four parts, it follows the stories of patients desperately seeking remedies; probes the for-profit clinics where unproven and unregulated treatments are being offered; takes you into the labs and hospital rooms where scientists are testing new therapies; and provides a comprehensive accounting of what California’s multi billion dollar bet on stem cells has achieved.

Our CEO Maria Millan shared her thoughts in response to some of the questions raised by this article.

Q: There have been many critics who say it’s taking too long for CIRM to deliver cures, and they expected more. What is your response to these people?

A: Many of us can relate that relief cannot come quickly enough for our relatives and friends who suffer from debilitating and devastating medical conditions— I believe that is why many of us are at CIRM, an organization whose mission is to accelerate stem cell treatments to patients with unmet medical needs. Through the years, we have enabled the creation of an incredible ecosystem of top scientists and researchers and partnered with patients and patient advocates to pursue this mission.  We continually strive to improve and to become more efficient  and we share the sense of urgency to harness the potential of stem cell biology to deliver relief to those in need.

Q: Given all of the differences between CIRM and the NIH, why do you think the reporter compared CIRM to the NIH?

A: The NIH is the largest health research funder world-wide, has been around a lot longer, has a much larger budget >$30B this past year alone and the NHLBI alone has a $3B annual budget—NHLBI is just one of the 27 NIH Institutes. The reason that CIRM was formed is that the advocates of Proposition 71 wanted to make sure that scientists and developers can pursue vital research opportunities that may not have access to funding by traditional funders, including the NIH. CIRM has a total budget of $3B available to fund research and support operations and we have been managing that budget since the passage of Proposition 71 in 2004.  If we consider  the number of stem cell trials for given available budget, CIRM has funded a disproportionately higher number of translational and clinical programs in stem cell and regenerative medicine. In fact, the NHLBI has entered into a collaboration with CIRM on their Cure Sickle Cell initiative because of CIRM’s specialization in funding and enabling cell-gene regenerative medicine research.  I take this as a validation of CIRM’s value proposition in this new area– acceleration, translation, and clinical trials.

Q: Given the visibility being given to stem cell tourism and direct to consumer marketing of unproven and unregulated therapies, what value does CIRM bring to patients?

A: CIRM is positioned as the trusted agency for delivering on high quality trials, for being on the side of patients for safe trials and treatments and is a credible partner for patient, industry, government stakeholders to tackle this issue of stem cell tourism. We only fund clinical trials backed by solid scientific data with FDA permission to test it in patients. We have funded research being conducted at top tier medical centers and created the Alpha Stem Cell Clinic Network to provide people with high quality clinical trials. We are remaining in close contact with our legislators, including Speaker Pro Tem Kevin Mullin, Chair of the Assembly Select Committee on Biotechnology, to evaluate potential ways to protect patients from illegitimate clinics while progress is being made with legitimate approaches.

Q: Do you feel that enough money is being put towards basic research?

A: If we had the budget to do so, we would like to be able to fund more discovery research as well as translational and clinical research.  However, approximately $880M CIRM funds have gone into basic research thus far.  CIRM has a specialized and very unique role that supports and fosters rigorous stem cell and regenerative medicine science but, CIRM has distinguished itself as an agency that specializes in accelerating the translation of this science to therapies for patients.

Dr. Millan also appeared with SF Chronicle reporter Erin Allday and UC Davis stem cell scientist Paul Knoepfler on a Facebook Live talk about the work of the stem cell agency.

Support cells have different roles in blood stem cell maintenance before and after stress

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Expression of pleiotrophin (green) in bone marrow blood vessels (red) and stromal cells (white) in normal mice (left), and in mice 24 hours after irradiation (right). UCLA Broad Stem Cell Research Center/Cell Stem Cell

A new study published in the journal Cell Stem Cell, reveals how different types of cells in the bone marrow are responsible for supporting blood stem cell maintenance before and after injury.

It was already well known in the field that two different cell types, namely endothelial cells (which line blood vessels) and stromal cells (which make up connective tissue, or tissue that provides structural support for any organ), are responsible for maintaining the population of blood stem cells in the bone marrow. However, how these cells and the molecules they secrete impact blood stem cell development and maintenance is not well understood.

Hematopoietic stem cells are responsible for generating the multiple different types of cells found in blood, from our oxygen carrying red blood cells to the many different types of white blood cells that make up our immune system.

Dr. John Chute’s group at UCLA had previously discovered that a molecule called pleiotrophin, or PTN, is important for promoting self-renewal of the blood stem cell population. They did not, however, understand which cells secrete this molecule and when.

To answer this question, the scientists developed mouse models that did not produce PTN in different types of bone marrow cells, such as endothelial cells and stromal cells. Surprisingly, they saw that the inability of stromal cells to produce PTN decreased the blood stem cell population, but deletion of PTN in endothelial cells did not affect the blood stem cell niche.

Even more interestingly, the researchers found that in animals that were subjected to an environmental stressor, in this case, radiation, the result was reversed: endothelial cell PTN was necessary for blood stem cell renewal, whereas stromal cell PTN was not. While an important part of the knowledge base for blood stem cell biology, the reason for this switch in PTN secretion at times of homeostasis and disease is still unknown.

As Dr. Chute states in a press release, this result could have important implications for cancer treatments such as radiation:

“It may be possible to administer modified, recombinant versions of pleiotrophin to patients to accelerate blood cell regeneration. This strategy also may apply to patients undergoing bone marrow transplants.”

Another important consideration to take away from this work is that animal models developed in the laboratory should take into account the possibility that blood stem cell maintenance and regeneration is distinctly controlled under healthy and disease state. In other words, cellular function in one state is not always indicative of its role in another state.

This work was partially funded by a CIRM Leadership Award.

 

 

Stem cell stories that caught our eye: Reprogramming cells in vivo may help heal ulcers, CIRM-funded clinical trial shows promise and a New report, clears up an old question.

Stem cell image of the week:  New Research out of the Salk Institute could bring us closer to reprogramming stem cells without taking them out of the body (Adonica Shaw)

Our stem cell image of the week could be a step towards reprogramming cells in vivo.

The image represents the first proof of principle for the successful regeneration of a functional organ (the skin) inside a mammal, by a technique known as AAV-based in vivo reprogramming. Epithelial (skin) tissues were generated by converting one cell type (red: mesenchymal cells) to another (green: basal keratinocytes) within a large ulcer in a laboratory mouse model.

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Photo courtesy of the Salk Institute

In large patches of ulcerous skin, surviving cells prioritize inflammation and wound closure. That’s what they’re programmed to do. Cells, on the other hand, can be reprogrammed in living tissue, wounded tissue, to expedite healing.

A group of scientists at the Salk Institute developed a new approach to cellular reprogramming. They found a way to directly convert the cells in an open wound into new skin cells. Their findings were published on Wednesday in Nature.

Reprogramming wound-resident cells could be useful for healing skin damage, countering the effects of aging, and helping us to better understand skin cancer. It could also supplant plastic surgery and the application of skin grafts as a way to treat large cutaneous ulcers, including those seen in people with severe burns, bedsores, or chronic diseases such as diabetes.

When an ulcer is especially large, it can be difficult for surgeons to graft enough skin. In these cases, researchers can isolate skin stem cells from a patient, grow them in the lab and transplant them back into the patient. However, such a procedure requires an extensive amount of time, which may put the patient’s life at risk and is sometimes not effective.

 “Our observations constitute an initial proof of principle for in vivo regeneration of an entire three-dimensional tissue like the skin, not just individual cell types as previously shown,” says Dr. Izpisua Belmonte. “This knowledge might not only be useful for enhancing skin repair but could also serve to guide in vivo regenerative strategies in other human pathological situations, as well as during aging, in which tissue repair is impaired.”

Positive news from a CIRM-funded clinical trial targeting a deadly blood cancer. (Kevin McCormack)  Multiple myeloma is a type of blood cancer where certain cells in the bone marrow grow out of control, crowding out the healthy cells and forming tumors. There is no cure but there are many treatments that can slow down or even halt the progression. Over time, however, many of those treatments lose their effectiveness and the cancer returns. Now a new CIRM-funded clinical trial targeting this kind of relapsing multiple myeloma is showing promise.

The trial, by Poseida Therapeutics, takes an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells. This product, called P-BCMA-101, is a stem cell memory chimeric antigen receptor T-cell (CAR-T).

In the first eleven patients treated there were no serious side effects and only one patient had a suspected case of cytokine release syndrome. That’s where large amounts of cytokines, immune substances, are rapidly released into the body causing fever, nausea, rapid heartbeat etc. However, even in this patient the symptoms quickly passed.

In a news release, Eric Ostertag, the CEO of Poseida said that even though the goal of this Phase 1 study was just to make sure it was safe and to identify the best dose to give patients, they have already seen a very good partial response in some patients.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

The clinical trial will eventually treat 40 patients with relapsing or remitting multiple myeloma and we will bring more results as they become available.

Techniques used in ecology help rewrite basic fact about blood stem cells (Todd Dubnicoff) It’s been over half a century since the first blood stem cell transplantation was performed. And yet, some fundamental facts about these cells – which give rise to all the cell types of our blood – have remained cloudy, like the number of blood stem cells present in the human body. This week, researchers at Wellcome Sanger Institute and Wellcome – MRC Cambridge Stem Cell Institute report that they’ve cleared up this long-lasting question.

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A blood cell colony grown from a single cell isolated from a 59-year-old man. Image Credit: Mairi Shepherd, Kent Lab

And the results were surprising. Using whole genome DNA sequencing and techniques found in ecology for tracking population sizes, the team determined that a healthy adult has between 50,000 and 200,000 blood stem cells at any given time. That’s about 10 times more than what was previously thought.

Dr. David Kent, a co-senior author on the report, described the implications of this discovery in a press release:

“This new approach is hugely flexible. Not only can we measure how many stem cells exist, we can also see how related they are to each other and what types of blood cells they produce. Applying this technique to samples from patients with blood cancers, we should now be able to learn how single cells outcompete normal cells to expand their numbers and drive a cancer.”

The study was published in Nature.

 

 

 

 

Saying goodbye to a good friend and a stem cell pioneer: Karl Trede

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Sometimes even courage and determination are not enough. Karl Trede had courage and determination in droves as he fought a 12 year battle against cancer. He recently lost that battle. But he remains an inspiration for all who knew him.

I got to know Karl for our 2016 Annual Report. Karl had been diagnosed with throat cancer in 2006. He underwent surgery to remove his vocal cords and the cancer seemed to be in remission. But then it returned, this time having spread to his lungs. His doctors said they had pretty much run out of options but would Karl consider trying something new, something no one else had tried before; stem cells.

Karl told me he didn’t hesitate.

“I said “sure”. I don’t believe I knew at the time that I was going to be the first one but I thought I’d give it a whirl. It was an experience for me. It was eye opening. I wasn’t real concerned about being the first, I figured I was going to have to go someday so I guess if I was the first person and something really went wrong then they’d definitely learn something. So, to me, that was kind of worth my time.”

Happily nothing went wrong and the team behind the therapy (Forty Seven Inc.) definitely learned something, they learned a lot about the correct dosage for patients; invaluable information in treating future patients.

Karl’s cancer was held at bay and he was able to do the one thing that brought him more pleasure than anything else; spend time with his family, his wife Vita, their four sons and their families. He doted on his grand kids and got to see them grow, and they got to know him.

Recently the cancer returned and this time there was no holding it at bay. To the end Karl remained cheerful and positive.

KARL poster

In our office is a huge poster of Karl with the words “Every Moment Counts” at the bottom. It’s a reminder to us why we come to work every day, why the people at Forty Seven Inc. and all the other researchers we support work so hard for years and years; to try and give people like Karl a few extra moments with his family.

At the top of the poster the word “Courage” is emblazoned across it. Karl has a huge smile on his face. Karl was certainly courageous, a stem cell pioneer willing to try something no one else ever had. He was also very modest.

Here is Karl speaking to our governing Board in December 2016

When I spoke to him in 2016, despite all he had gone through in his fight against cancer, he said he had no regrets:

“I consider myself very fortunate. I’m a lucky guy.”

Those of us who got to spend just a little time with Karl know that we were the lucky ones.

Our hearts go out to his family and friends for their loss.

 

 

How small talk led to a big break; a summer internship at CIRM

At CIRM, California’s Stem Cell Agency, we are fortunate to work with some amazing people. This summer we added another name that list when Melissa Cairos joined us for an internship. Melissa is now on to the next part of her adventure, as a policy wonk in Washington DC., but before she left we asked her to write about her experiences, and thoughts after her time at the Stem Cell Agency.

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Melissa Cairos

In January of 2018, I had a casual conversation with a woman, whom I had never met before, at a high school basketball game. Through small talk about my studies in school and my career interests for the future, the woman suggested I may be interested in her work because it seemed to be aligned with what I wanted to do. Her work happened to be at CIRM and she happened to be Maria Millan, the President and CEO.

Interestingly, I had never heard of CIRM (the California Institute for Regenerative Medicine) and had limited knowledge of regenerative medicine. But, I had dedicated a semester in spring of 2015 to analyzing and lobbying for the 21st Century Cures Act. I engaged in that work because I believe in the importance of investing in, and expediting the regulatory process for, lifesaving medical innovations, so that they can be accessed faster by patients and at a lower cost. The 21st Century Cures Act has since become law and has created incredible opportunities for both CIRM and the entire field of regenerative medicine.

Since joining CIRM, I have been able to continue with similar work by analyzing legislation, policies and regulations that affect patients’ abilities to access regenerative medicine therapies and our grantees’ abilities to receive reimbursement for their therapies. Because the stem cell and gene therapies CIRM’s grantees are coming up with are so new and innovative, I quickly realized that the legislative, policy and regulatory solutions for them needed to reflect that innovative spirit.

Working alongside Geoff Lomax, (the Senior Officer for CIRM Strategic Infrastructures)  my manager and mentor, we identified a number of potential barriers to access and reimbursement and tried to come up with policy solutions to address them.

For one project, we looked at the high cost of regenerative medicine therapies. Because high cost affects both patient access and potential reimbursement problems for the companies that develop those therapies we felt it was essential to try and come up with policy solutions to address these issues. To do this, we studied the traditional payment structure for drugs and medical devices and found it inappropriate for regenerative medicine in most cases.

This is because regenerative medicine requires a one-time high cost payment, but the regenerative medicine treatments/cures would eliminate long term costs including: previous treatment cost, complications from that treatment, progression of disease cost, hospitalizations, disability, quality of life, co-morbidities, disease effect on longevity etc. Thus, we proposed that payment models for regenerative medicine should consider their unique value benefits, such as the number of additional years of life the treatment added, and the overall cost-effectiveness of a one-time treatment compared to years of  treatment. With this in mind, we suggested innovative payment models that accounted for these factors and further proposed changes that need to be made so that different manufacturers and payors can engage in innovative financing agreements.

Through my work at CIRM, I found that what makes regenerative medicine unique is that it not only offers new ways of treating previously untreatable diseases, but it has additional benefits or value. Not only the economic value, but also the human value, as regenerative medicine offers patients with life threatening or painful chronic diseases a solution that will change their lives and the lives of their families for the better. Through this understanding, I grew an incredible appreciation for CIRM, for not only being a great place to work with incredibly talented and kind people, but also an incredibly unique government agency that reflected the value and innovative spirit of the research it supports.

I am so grateful that I met Maria at that basketball game and got the opportunity to support CIRM in adding value to California in my role this summer as a Policy Fellow. I plan to return to California in the future and work in the health policy field to further support programs, policies, and/or agencies, like CIRM, that bring so much value to this state.