Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

 

TITLE

 

INSTITUTION

CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

 

U.C San Diego

 

$1,393,200

 

DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

 

U.C. Los Angeles

 

$1,404,000

DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

 

U.C. San Francisco

 

$900,000

DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

 

Salk Institute

 

$1,637,209

DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

 

City of Hope

 

$1,381,104

DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

 

Gladstone Institutes

 

$1,553,923

DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

 

U.C. San Diego

 

$865,282

DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

 

Stanford University

 

$865,282

 

 

A road trip to the Inland Empire highlights a hot bed of stem cell research

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Gillian Wilson, Interim Vice Chancellor, Research, UC Riverside welcomes people to the combined Research Roadshow and Patient Advocate event

It took us longer than it should have to pay a visit to California’s Inland Empire, but it was definitely worth the wait. Yesterday CIRM’s Roadshow went to the University of California at Riverside (UCR) to talk to the community there – both scientific and public – about the work we are funding and the progress being made, and to hear from them about their hopes and plans for the future.

As always when we go on the road, we learn so much and are so impressed by everyone’s passion and commitment to stem cell research and their belief that it’s changing the face of medicine as we know it.

Dr. Deborah Deas, the Dean of the UC Riverside School of Medicine and a CIRM Board member, kicked off the proceedings by saying:

“Since CIRM was created in 2004 the agency has been committed to providing the technology and research to meet the unmet needs of the people of California.

On the Board I have been impressed by the sheer range and number of diseases targeted by the research CIRM is funding. We in the Inland Empire are playing our part. With CIRM’s help we have developed a strong program that is doing some exciting work in discovery, education and translational research.”

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CIRM’s Dr. Maria Millan at the Roadshow Patient Advocate event

CIRM’s President and CEO, Dr. Maria T. Millan, and our Board Chair, Jonathan Thomas then gave a quick potted history of CIRM and the projects we are funding. They highlighted how we are creating a pipeline of products from the Discovery, or basic level of research, through to the 45 clinical trials we are funding.

They also talked about the Alpha Clinic Network, based at six highly specialized medical centers around California, that are delivering stem cell therapies and sharing the experiences and knowledge learned from these trials to improve their ability to help patients and advance the field.

Researchers from both UCR then gave a series of brief snapshots of the innovative work they are doing:

  • Looking at new, more efficient and effective ways of expanding the number of human embryonic stem cells in the laboratory to create the high volume of cells needed for therapies.
  • Using biodegradable materials to help repair and regenerate tissue for things as varied as bone and cartilage repair or nerve restoration.
  • Exploring the use of epigenetic factors, things that switch genes on and off, to try and find ways to make repairs inside the body, rather than taking the cells outside the body, re-engineering them and returning them to the body. In essence, using the body as its own lab to manufacture replacement.

Another CIRM Board member, Linda Malkas, talked about the research being done at City of Hope (COH), where she is the associate chair of the Department of Molecular and Cellular Biology, calling it an “engine for discovery that has created the infrastructure and attracted people with an  amazing set of skills to bring forward new therapeutics for patients.”

She talked about how COH is home to one of the first Alpha Clinics that CIRM funded, and that it now has 27 active clinical trials, with seven more pending and 11 more in the pipeline.

“In my opinion this is one of the crown jewels of the CIRM program. CIRM is leading the nation in showing how to put together a network of specialized clinics to deliver these therapies. The National Institutes of Health (NIH) came to CIRM to learn from them and to talk about how to better move the most promising ideas and trials through the system faster and more efficiently.”

Dr. Malkas also celebrated the partnership between COH and UCR, where they are collaborating on 19 different projects, pooling their experience and expertise to advance this research.

Finally, Christine Brown, PhD, talked about her work using chimeric antigen receptor (CAR) T cells to fight cancer stem cells. In this CIRM-funded clinical trial, Dr. Brown hopes to re-engineer a patient’s T cells – a key cell of the immune system – to recognize a target protein on the surface of brain cancer stem cells and kill the tumors.

It was a packed event, with an overflow group watching on monitors outside the auditorium. The questions asked afterwards didn’t just focus on the research being done, but on research that still needs to be done.

One patient advocate couple asked about clinics offering stem cell therapies for Parkinson’s disease, wondering if the therapies were worth spending more than $10,000 on.

Dr. Millan cautioned against getting any therapy that wasn’t either approved by the Food and Drug Administration (FDA) or wasn’t part of a clinical trial sanctioned by the FDA. She said that in the past, these clinics were mostly outside the US (hence the term “stem cell tourism”) but increasingly they are opening up centers here in the US offering unproven and unapproved therapies.

She said there are lots of questions people need to ask before signing up for a clinical trial. You can find those questions here.

The visit was a strong reminder that there is exciting stem cell research taking place all over California and that the Inland Empire is a key player in that research, working on projects that could one day have a huge impact in changing people’s lives, even saving people’s lives.

 

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

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I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

Stem Cell Agency invests in stem cell therapies targeting sickle cell disease and solid cancers

Today CIRM’s governing Board invested almost $10 million in stem cell research for sickle cell disease and patients with solid cancer tumors.

Clinical trial for sickle cell disease

City of Hope was awarded $5.74 million to launch a Phase 1 clinical trial testing a stem cell-based therapy for adult patients with severe sickle cell disease (SCD). SCD refers to a group of inherited blood disorders that cause red blood cells to take on an abnormal, sickle shape. Sickle cells clog blood vessels and block the normal flow of oxygen-carrying blood to the body’s tissues. Patients with SCD have a reduced life expectancy and experience various complications including anemia, stroke, organ damage, and bouts of excruciating pain.

A mutation in the globlin gene leads to sickled red blood cells that clog up blood vessels

CIRM’s President and CEO, Maria T. Millan, explained in the Agency’s news release:

Maria T. Millan

“The current standard of treatment for SCD is a bone marrow stem cell transplant from a genetically matched donor, usually a close family member. This treatment is typically reserved for children and requires high doses of toxic chemotherapy drugs to remove the patient’s diseased bone marrow. Unfortunately, most patients do not have a genetically matched donor and are unable to benefit from this treatment. The City of Hope trial aims to address this unmet medical need for adults with severe SCD.”

The proposed treatment involves transplanting blood-forming stem cells from a donor into a patient who has received a milder, less toxic chemotherapy treatment that removes some but not all of the patient’s diseased bone marrow stem cells. The donor stem cells are depleted of immune cells called T cells prior to transplantation. This approach allows the donor stem cells to engraft and create a healthy supply of non-diseased blood cells without causing an immune reaction in the patient.

Joseph Rosenthal, the Director of Pediatric Hematology and Oncology at the City of Hope and lead investigator on the trial, mentioned that CIRM funding made it possible for them to test this potential treatment in a clinical trial.

“The City of Hope transplant program in SCD is one of the largest in the nation. CIRM funding will allow us to conduct a Phase 1 trial in six adult patients with severe SCD. We believe this treatment will improve the quality of life of patients while also reducing the risk of graft-versus-host disease and transplant-related complications. Our hope is that this treatment can be eventually offered to SCD patients as a curative therapy.”

This is the second clinical trial for SCD that CIRM has funded – the first being a Phase 1 trial at UCLA treating SCD patients with their own genetically modified blood stem cells. CIRM is also currently funding research at Children’s Hospital of Oakland Research Institute and Stanford University involving the use of CRISPR gene editing technologies to develop novel stem cell therapies for SCD patients.

Advancing a cancer immunotherapy for solid tumors

The CIRM Board also awarded San Diego-based company Fate Therapeutics $4 million to further develop a stem cell-based therapy for patients with advanced solid tumors.

Fate is developing FT516, a Natural Killer (NK) cell cancer immunotherapy derived from an engineered human induced pluripotent stem cell (iPSC) line. NK cells are part of the immune system’s first-line response to infection and diseases like cancer. Fate is engineering human iPSCs to express a novel form of a protein receptor, called CD16, and is using these cells as a renewable source for generating NK cells. The company will use the engineered NK cells in combination with an anti-breast cancer drug called trastuzumab to augment the drug’s ability to kill breast cancer cells.

“CIRM sees the potential in Fate’s unique approach to developing cancer immunotherapies. Different cancers require different approaches that often involve a combination of treatments. Fate’s NK cell product is distinct from the T cell immunotherapies that CIRM also funds and will allow us to broaden the arsenal of immunotherapies for incurable and devastating cancers,” said Maria Millan.

Fate’s NK cell product will be manufactured in large batches made from a master human iPSC line. This strategy will allow them to treat a large patient population with a well characterized, uniform cell product.

The award Fate received is part of CIRM’s late stage preclinical funding program, which aims to fund the final stages of research required to file an Investigational New Drug (IND) application with the US Food and Drug Administration. If the company is granted an IND, it will be able to launch a clinical trial.

Scott Wolchko, President and CEO of Fate Therapeutics, shared his company’s goals for launching a clinical trial next year with the help of CIRM funding:

“Fate has more than a decade of experience in developing human iPSC-derived cell products. CIRM funding will enable us to complete our IND-enabling studies and the manufacturing of our clinical product. Our goal is to launch a clinical trial in 2019 using the City of Hope CIRM Alpha Stem Cell Clinic.”

California gets first royalty check from Stem Cell Agency investments

COH image

CIRM recently shared in a little piece of history. The first royalty check, based on CIRM’s investment in stem cell research, was sent to the California State Treasurer’s office from City of Hope. It’s the first of what we hope will be many such checks, helping repay, not just the investment the state made in the field, but also the trust the voters of California showed when they created CIRM.

The check, for $190,345.87, was for a grant we gave City of Hope back in 2012 to develop a therapy for glioblastoma, one of the deadliest forms of brain cancer. That has led to two clinical trials and a number of offshoot inventions that were subsequently licensed to a company called Mustang Bio.

Christine Brown, who is now the principal investigator on the project, is quoted in a front page article in the San Francisco Chronicle, on the significance of the check for California:

“This is an initial payment for the recognition of the potential of this therapy. If it’s ultimately approved by the FDA as a commercial product, this could be a continued revenue source.”

In the same article, John Zaia, Director of the City of Hope Alpha Stem Cell Clinic, says this also reflects the unique nature of CIRM:

“I think this illustrates that a state agency can actually fund research in the private community and get a return on its investment. It’s something that’s not done in general by other funding agencies such as the National Institutes of Health, and this is a proof of concept that it can work.”

Maria Millan, CIRM’s President & CEO, says the amount of the payment is not the most significant part of this milestone – after all CIRM has invested more than $2.5 billion in stem cell research since 2004. She says the fact that we are starting to see a return on the investment is important and reflects some of the many benefits CIRM brings to the state.

“It’s a part of the entire picture of the return to California. In terms of what it means to the health of Californians, and access to these transformative treatments, as well as the fact that we are growing an industry.”

 

Taking a new approach to fighting a deadly brain cancer

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Christine Brown, Ph.D., City of Hope researcher

CIRM’s 2017 Annual Report will be going live online very soon. In anticipation of that we are highlighting some of the key elements from the report here on the Stem Cellar.

One of the most exciting new approaches in targeting deadly cancers is chimeric antigen receptor (CAR) T-cell therapy, using the patient’s own immune system cells that have been re-engineered to help them fight back against the tumor.

Today we are profiling City of Hope’s Christine Brown, Ph.D., who is using CAR-T cells in a CIRM-funded Phase 1 clinical trial for an aggressive brain cancer called malignant glioma.

“Brain tumors are the hardest to treat solid tumors. This is a project that CIRM has supported from an early, pre-clinical stage. What was exciting was we finished our first milestone in record time and were able to translate that research out of the lab and into the clinic. That really allowed us to accelerate treatment to glioblastoma patients.

I think there are glimmers of hope that immune based therapies and CAR-T based therapies will revolutionize therapy for patients with brain tumors. We’ve seen evidence that these cells can travel to the central nervous system and eliminate tumors in the brain.

We now have evidence that this approach produces a powerful, therapeutic response in one group of patients. We are looking at why other patients don’t respond as well and the CIRM funding enables us to ask the questions that will, we hope, provide the answers.

Because our clinical trial is a being carried out at the CIRM-supported City of Hope Alpha Stem Cell Clinic this is a great example of how CIRM supports all the different ways of advancing therapy from early stage research through translation and into clinical trials in the CIRM Alpha Clinic network.

There are lots of ways the tumor tries to evade the immune system and we are looking at different approaches to combine this therapy with different approaches to see which combination will be best.

It’s a challenging problem and it’s not going to be solved with one approach. If it were easy we’d have solved it by now. That’s why I love science, it’s one big puzzle about how do we understand this and how do we make this work.

I don’t think we would be where we are at without CIRM’s support, it really gave the funding to bring this to the next level.”

Dr. Brown’s work is also creating interest among investors. She recently partnered with Mustang Bio in a $94.5 million agreement to help advance this therapy.

CIRM-Funded Research Makes Multiple Headlines this Week

When it rains it pours.

This week, multiple CIRM-funded studies appeared in the news, highlighting the exciting progress our Agency is making towards funding innovative stem cell research and promoting the development of promising stem cell therapies for patients.

Below are highlights.


Fate Therapeutics Partners with UC San Diego to Develop Cancer Immunotherapy

Last week, Dr. Dan Kaufman and his team at UC San Diego, received a $5.15 million therapeutic translational research award from CIRM to advance the clinical development of a stem cell-derived immunotherapy for acute myelogenous leukemia (AML), a rare form of blood cancer.

Today, it was announced that the UCSD team is entering into a research collaboration with a San Diego biopharmaceutical company Fate Therapeutics to develop a related immunotherapy for blood cancers. The therapy consists of immune cells called chimeric antigen receptor-targeted natural killer (CAR NK) cells that can target tumor cells and stop their growth. Fate Therapeutics has developed an induced pluripotent stem cell (iPSC) platform to develop and optimize CAR NK cell therapies targeting various cancers.

According to an article by GenBio, this new partnership is already bearing fruit.

“In preclinical studies using an ovarian cancer xenograft model, Dr. Kaufman and Fate Therapeutics had shown that a single dose of CAR-targeted NK cells derived from iPSCs engineered with the CAR construct significantly inhibited tumor growth and increased survival compared to NK cells containing a CAR construct commonly used for T-cell immunotherapy.”

 


City of Hope Brain Cancer Trial Featured as a Key Trial to Watch in 2018

Xconomy posted a series this week forecasting Key Clinical Data to look out for next year. Today’s part two of the series mentioned a recent CIRM-funded trial for glioblastoma, an aggressive, deadly brain cancer.

Christine Brown and her team at the City of Hope are developing a CAR-T cell therapy that programs a patient’s own immune cells to specifically target and kill cancer cells, including cancer stem cells, in the brain. You can read more about this therapy and the Phase 1 trial on our website.

Alex Lash, Xconomy’s National Biotech Editor, argued that good results for this trial would be a “huge step forward for CAR-T”.

Alex Lash

“While CAR-T has proven its mettle in certain blood cancers, one of the biggest medical questions in biotech is whether the killer cells can also eat up solid tumors, which make up the majority of cancer cases. Glioblastoma—an aggressive and usually incurable brain cancer—is a doozy of a solid tumor.”


ViaCyte Receives Innovative New Product Award for Type 1 Diabetes

Last week, San Diego-based ViaCyte was awarded the “Most Innovative New Product Award” by CONNECT, a start-up accelerator focused on innovation, for its PEC-Direct product candidate. The product is a cell-based therapy that’s currently being tested in a CIRM-funded clinical trial for patients with high-risk type 1 diabetes.

In a company news release published today, ViaCyte’s CEO Paul Laikind commented on what the award signifies,

Paul Laikind

“This award acknowledges how ViaCyte has continually broken new ground in stem cell research, medical device engineering, and cell therapy scaling and manufacturing. With breakthrough technology, clinical stage product candidates, an extensive intellectual property estate, and a strong and dedicated team, ViaCyte has all the pieces to advance a transformative new life-saving approach that could help hundreds of thousands of people with high-risk type 1 diabetes around the world.”

Inspiring the next generation of stem cell scientists

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SPARK students at the 2017 Annual Meeting at the City of Hope.

“The technological breakthroughs that will be happening over the next few years – it’s your generation of scientists that will make this happen.”

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John Zaia

Dr. John Zaia, the Director of City of Hope’s Center for Gene Therapy, directed these words to a group of 55 talented high school students attending the 2017 CIRM SPARK meeting.

SPARK stands for Summer Program to Accelerate Regenerative Medicine Knowledge. Students in the program spend their summer tackling difficult stem cell research projects in the lab, attending scientific workshops and lectures, and participated in patient engagement activities.

At the end of the summer, SPARK students from seven different programs at institutions and universities across California attend the annual SPARK meeting. At this gathering, students present their research to researchers and their families. They also hear about the progress in developing stem cell therapies from scientists and doctors and about exciting career paths in science and STEM fields from SPARK alumni.

The program is an excellent way for high school students to get their “research feet” wet. They are trained in basic lab and stem cell techniques and are assigned to a mentor who guides them through their research project.

Many of the students who participate in our SPARK programs go on to prestigious colleges to pursue degrees in science, medicine, and engineering. You can read some of these stories on our blog here and here.

At CIRM, we are invested in educating the next generation of stem cell scientists. Our Vice-Chair of the CIRM Board, Sen. Art Torres, said it perfectly at this year’s SPARK meeting:

“I just want to thank you for being part of this program. We are very proud of each and every one of you and we expect great things in the future.”

Check out this short video, produced by City of Hope, which features highlights from our 2017 SPARK meeting at the City of Hope. As you will see, this program is not only fun, but is a one-in-a-lifetime experience.

If you’re interested in learning more about our SPARK program or applying to be a SPARK intern, visit our website for more information. SPARK programs typically accept applications in December or early in the year. Each program has its own eligibility requirements and application process and you can find out that information on the individual SPARK program websites listed on our CIRM SPARK webpage.

CIRM Board Appoints Dr. Maria Millan as President and CEO

Dr. Maria Millan, President and CEO of CIRM, at the September Board meeting. (Todd Dubnicoff, CIRM)

Yesterday was a big day for CIRM. Our governing Board convened for its September ICOC meeting and appointed Dr. Maria Millan as our new President and CEO. Dr. Millan has been serving as the Interim President/CEO since July, replacing former President Dr. Randal Mills.

Dr. Millan has been at CIRM since 2012 and was instrumental in the development of CIRM’s infrastructure programs including the Alpha Stem Cell Clinics Network and the agency’s Strategic Plan, a five-year plan that lays out our agency’s goals through 2020. Previously, Dr. Millan was the Vice President of Therapeutics at CIRM, helping the agency fund 23 new clinical trials since the beginning of 2016.

The Board vote to appoint Dr. Millan as President and CEO was unanimous and enthusiastic. Chairman of the Board, Jonathan Thomas, shared the Board’s sentiments when he said,

“Dr. Millan is absolutely the right person for this position. Having seen Dr. Millan as the Interim CEO of CIRM for three months and how she has operated in that position, I am even more enthusiastic than I was before. I am grateful that we have someone of Maria’s caliber to lead our Agency.”

Dr. Millan has pursued a career devoted to helping patients. Before working at CIRM, she was an organ transplant surgeon and researcher and served as an Associate Professor of Surgery and Director of the Pediatric Organ Transplant Program at Stanford University. Dr. Millan was also the Vice President and Chief Medical Officer at StemCells, Inc.

In her permanent role as President, Dr. Millan is determined to keep CIRM on track to achieve the goals outlined in our strategic plan and to achieve its mission to accelerate treatments to patients with unmet needs. She commented in a CIRM press release,

“I joined the CIRM team because I wanted to make a difference in the lives of patients. They are the reason why CIRM exists and why we fund stem cell research. I am humbled and very honored to be CIRM’s President and look forward to further implementing our agency’s Strategic Plan in the coming years.”

The Board also voted to fund two new Alpha Stem Cell Clinics at UC Davis and UC San Francisco and five new clinical trials. Three of the clinical awards went to projects targeting cancer.

The City of Hope received $12.8 million to fund a Phase 1 trial targeting malignant gliomas (an aggressive brain cancer) using CAR-T cell therapy. Forty Seven Inc. received $5 million for a Phase 1b clinical trial treating acute myeloid leukemia. And Nohla Therapeutics received $6.9 million for a Phase 2 trial testing a hematopoietic stem cell and progenitor cell therapy to help patients suffering from neutropenia, a condition that leaves people susceptible to deadly infections, after receiving chemotherapy for acute myeloid leukemia.

The other two trials target diabetes and end stage kidney failure. ViaCyte, Inc. was awarded $20 million to fund a Phase 1/2 clinical trial to test its PEC-Direct islet cell replacement therapy for high-risk type 1 diabetes. Humacyte Inc. received $14.1 million to fund a Phase 3 trial that is comparing the performance of its acellular bioengineered vessel with the current standard of dialysis treatment for kidney disease patients.

The Board also awarded $5.2 million to Stanford Medicine for a late stage preclinical project that will use CRISPR gene editing technology to correct the sickle cell disease mutation in blood-forming stem cells to treat patients with sickle cell disease. This award was particularly well timed as September is Sickle Cell Awareness month.

The Stanford team, led by Dr. Matthew Porteus, hopes to complete the final experiments required for them to file an Investigational New Drug (IND) application with the FDA so they can be approved to start a clinical trial hopefully sometime in 2018. You can read more about Dr. Porteus’ work here and you can read our past blogs featuring Sickle Cell Awareness here and here.

With the Board’s vote yesterday, CIRM’s clinical trial count rises to 40 funded trials since its inception. 23 of these trials were funded after the launch of our Strategic Plan bringing us close to the half way point of funding 50 new clinical trials by 2020. With more “shots-on-goal” CIRM hopes to increase the chances that one of these trials will lead to an FDA-approved therapy for patients.


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Stem Cell Stories That Caught our Eye: Duchenne muscular dystrophy and short telomeres, motor neurons from skin, and students today, stem cell scientists tomorrow

Short telomeres associated with Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a severe muscle wasting disease that typically affects young men. There is no cure for DMD and the average life expectancy is 26. These are troubling facts that scientists at the University of Pennsylvania are hoping to change with their recent findings in Stem Cell Reports.

Muscle stem cells with telomeres shown in red. (Credit: Penn Medicine)

The team discovered that the muscle stem cells in DMD patients have shortened telomeres, which are the protective caps on the ends of chromosomes that prevent the loss of precious genetic information during cell division. Each time a cell divides, a small section of telomere is lost. This typically isn’t a problem because telomeres are long enough to protect cells through many divisions.

But it turns out this is not the case for the telomeres in the muscle stem cells of DMD patients. Because DMD patients have weak muscles, they experience constant muscle damage and their muscle stem cells have to divide more frequently (basically non-stop) to repair and replace muscle tissue. This is bad news for the telomeres in their muscle stem cells. Foteini Mourkioti, senior author on the study, explained in a news release,

“We found that in boys with DMD, the telomeres are so short that the muscle stem cells are probably exhausted. Due to the DMD, their muscle stem cells are constantly repairing themselves, which means the telomeres are getting shorter at an accelerated rate, much earlier in life. Future therapies that prevent telomere loss and keep muscle stem cells viable might be able to slow the progress of disease and boost muscle regeneration in the patients.”

With these new insights, Mourkioti and his team believe that targeting muscle stem cells before their telomeres become too short is a good path to pursue for developing new treatments for DMD.

“We are now looking for signaling pathways that affect telomere length in muscle stem cells, so that in principle we can develop drugs to block those pathways and maintain telomere length.”

Making Motor Neurons from Skin.

Skin cells and brain cells are like apples and oranges, they look completely different and have different functions. However, in the past decade, researchers have developed methods to transform skin cells into neurons to study neurodegenerative disorders and develop new strategies to treat brain diseases.

Scientists at Washington University School of Medicine in St. Louis published new findings on this topic yesterday in the journal Cell Stem Cell. In a nut shell, the team discovered that a specific combination of microRNAs (molecules involved in regulating what genes are turned on and off) and transcription factors (proteins that also regulate gene expression) can turn human skin cells into motor neurons, which are the brain cells that degenerate in neurodegenerative diseases like ALS, also known as Lou Gehrig’s disease.

Human motor neurons made from skin. (Credit: Daniel Abernathy)

This magical cocktail of factors told the skin cells to turn off genes that make them skin and turn on genes that transformed them into motor neurons. The scientists used skin cells from healthy individuals but will soon use their method to make motor neurons from patients with ALS and other motor neuron diseases. They are also interested in generating neurons from older patients who are more advanced in their disease. Andrew Yoo, senior author on the study, explained in a news release,

“In this study, we only used skin cells from healthy adults ranging in age from early 20s to late 60s. Our research revealed how small RNA molecules can work with other cell signals called transcription factors to generate specific types of neurons, in this case motor neurons. In the future, we would like to study skin cells from patients with disorders of motor neurons. Our conversion process should model late-onset aspects of the disease using neurons derived from patients with the condition.”

This research will make it easier for other scientists to grow human motor neurons in the lab to model brain diseases and potentially develop new treatments. However, this is still early stage research and more work should be done to determine whether these transformed motor neurons are the “real deal”. A similar conclusion was shared by Julia Evangelou Strait, the author of the Washington University School of Medicine news release,

“The converted motor neurons compared favorably to normal mouse motor neurons, in terms of the genes that are turned on and off and how they function. But the scientists can’t be certain these cells are perfect matches for native human motor neurons since it’s difficult to obtain samples of cultured motor neurons from adult individuals. Future work studying neuron samples donated from patients after death is required to determine how precisely these cells mimic native human motor neurons.”

Students Today, Scientists Tomorrow.

What did you want to be when you were growing up? For Benjamin Nittayo, a senior at Cal State University Los Angeles, it was being a scientist researching a cure for acute myeloid leukemia (AML), a form of blood cancer that took his father’s life. Nittayo is making his dream into a reality by participating in a summer research internship through the Eugene and Ruth Roberts Summer Student Academy at the City of Hope in Duarte California.

Nittayo has spent the past two summers doing cancer research with scientists at the Beckman Research Institute at City of Hope and hopes to get a PhD in immunology to pursue his dream of curing AML. He explained in a City of Hope news release,

“I want to carry his memory on through my work. Being in this summer student program helped me do that. It influenced the kind of research I want to get into as a scientist and it connected me to my dad. I want to continue the research I was able to start here so other people won’t have to go through what I went through. I don’t wish that on anybody.”

The Roberts Academy also hosts high school students who are interested in getting their first experience working in a lab. Some of these students are part of CIRM’s high school educational program Summer Program to Accelerate Regenerative Medicine Knowledge or SPARK. The goal of SPARK is to train the next generation of stem cell scientists in California by giving them hands-on training in stem cell research at leading institutes in the state.

This year, the City of Hope hosted the Annual SPARK meeting where students from the seven different SPARK programs presented their summer research and learned about advances in stem cell therapies from City of Hope scientists.

Ashley Anderson, a student at Mira Costa High School in Manhattan Beach, had the honor of giving the City of Hope SPARK student talk. She shared her work on Canavan’s disease, a progressive genetic disorder that damages the brain’s nerve cells during infancy and can cause problems with movement and muscle weakness.

Under the guidance of her mentor Yanhong Shi, Ph.D., who is a Professor of Developmental and Stem Cell Biology at City of Hope, Ashley used induced pluripotent stem cells (iPSCs) from patients with Canavan’s to generate different types of brain cells affected by the disease. Ashley helped develop a protocol to make large quantities of neural progenitor cells from these iPSCs which the lab hopes to eventually use in clinical trials to treat Canavan patients.

Ashley has always been intrigued by science, but thanks to SPARK and the Roberts Academy, she was finally able to gain actual experience doing science.

“I was looking for an internship in biosciences where I could apply my interest in science more hands-on. Science is more than reading a textbook, you need to practice it. That’s what SPARK has done for me. Being at City of Hope and being a part of SPARK was amazing. I learned so much from Dr. Shi. It’s great to physically be in a lab and make things happen.”

You can read more about Ashley’s research and those of other City of Hope SPARK students here. You can also find out more about the educational programs we fund on our website and on our blog (here and here).