Yanhong Shi, Ph.D., Beckman Research Institute of City of Hope.
Progress is being made to treat cancer patients suffering from degenerative brain diseases.
Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States, have developed universal donor stem cells that could one day provide lifesaving therapy to children with lethal brain conditions such as Canavan disease, as well as other degenerative diseases like Alzheimer’s and multiple sclerosis.
Funding from the California Institute for Regenerative Medicine (CIRM) helped to advance the research which lays the foundation to apply donor stem cells not only for those with brain diseases, but also for patients undergoing chemotherapy and experiencing debilitating cognitive or motor difficulties.
“The off-the-shelf approach City of Hope is taking can easily be extended to improve the quality of life of cancer patients who are experiencing cognitive impairment or impaired motor function as a side effect of chemotherapy or radiation,” said Yanhong Shi, Ph.D., chair of the Department of Neurodegenerative Diseases and the Herbert Horvitz Professor in Neuroscience at Beckman Research Institute of City of Hope.
A First-in-Kind Approach
While the previous research has focused on creating cell therapies from a patient’s own cells, this is the first time stem cells have been engineered to become universal donors for cell therapy targeting diseases of the central nervous system.
This technique allows engineered hypoimmunogenic cells from a healthy donor to be transplanted into a humanized disease model without activating the immune system to kill the foreign therapeutic.
This approach could potentially improve the quality of life for cancer patients facing debilitating side effects from chemotherapy and radiation therapy by providing them options for treatment earlier in their journey.
About CIRM’s Alpha Clinics Network
As one of nine CIRM-funded Alpha Clinic sites across California, City of Hope will continue to leverage its expertise in brain science to identify ways to aid patients who suffer from fatal or chronic conditions.
The CIRM-supported Alpha Clinics Network specializes in delivering stem cell and gene therapy clinical trial opportunities and treatments to patients. The network supports both CIRM-funded clinical trials and those funded by academic and industry sponsors.
Learn more about CIRM’s Alpha Clinics here. To learn more about the City of Hope research, click here.
This brings the total number of CIRM funded clinical trials to 83.
$11,999,984 was awarded to Dr. Jana Portnow at the Beckman Research Institute of City of Hope. They are using Neural stem cells (NSCs) as a form of delivery vehicle to carry a cancer-killing virus that specifically targets brain tumor cells.
Glioblastoma is the most common malignant primary brain tumor in adults and each year about 12,000 Americans are diagnosed. The 5-year survival rate is only about 10%.
The current standard of care involves surgically removing the tumor followed by radiation, chemotherapy, and alternating electric field therapy. Despite these treatments, survival remains low.
The award to Dr. Portnow will fund a clinical trial to assess the safety and effectiveness of this stem cell-based treatment for Glioblastoma.
The Board also awarded $3,111,467 to Dr. Boris Minev of Calidi Biotherapeutics. This award is in the form of a CLIN1 grant, with the goal of completing the testing needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial in people.
This project uses donor fat-derived mesenchymal stem cells that have been loaded with oncolytic virus to target metastatic melanoma, triple negative breast cancer, and advanced head & neck squamous cell carcinoma.
“There are few options for patients with advanced solid tumor cancers such as glioblastoma, melanoma, breast cancer, and head & neck cancer,” says Maria T. Millan, M.D., President and CEO of CIRM. “Surgical resection, chemotherapy and radiation are largely ineffective in advanced cases and survival typically is measured in months. These new awards will support novel approaches to address the unmet medical needs of patients with these devastating cancers.”
The CIRM Board also voted to approve awarding $71,949,539 to expand the CIRM Alpha Clinics Network. The current network consists of six sites and the Board approved continued funding for those and added an additional three sites. The funding is to last five years.
The goal of the Alpha Clinics award is to expand existing capacities for delivering stem cell, gene therapies and other advanced treatment to patients. They also serve as a competency hub for regenerative medicine training, clinical research, and the delivery of approved treatments.
Each applicant was required to submit a plan for Diversity, Equity and Inclusion to support and facilitate outreach and study participation by underserved and disproportionately affected populations in the clinical trials they serve.
The successful applicants are:
Application
Program Title
Institution/Principal Investigator
Amount awarded
INFR4-13579
The Stanford Alpha Stem Cell Clinic
Stanford University – Matthew Porteus
$7,997,246
INFR4-13581
UCSF Alpha Stem Cell Clinic
U.C. San Francisco – Mark Walters
$7,994,347
INFR4-13586
A comprehensive stem cell and gene therapy clinic to advance new therapies for a diverse patient population in California
Cedars-Sinai Medical Center – Michael Lewis
$7,957,966
INFR4-13587
The City of Hope Alpha Clinic: A roadmap for equitable and inclusive access to regenerative medicine therapies for all Californians
City of Hope – Leo Wang
$8,000,000
INFR4-13596
Alpha Stem Cell Clinic for Northern and Central California
U.C. Davis – Mehrdad Abedi
$7,999,997
INFR4-13685
Expansion of the Alpha Stem Cell and Gene Therapy Clinic at UCLA
U.C. Los Angeles – Noah Federman
$8,000,000
INFR4-13878
Alpha Clinic Network Expansion for Cell and Gene Therapies
University of Southern California – Thomas Buchanan
$7,999,983
INFR4-13952
A hub and spoke community model to equitably deliver regenerative medicine therapies to diverse populations across four California counties
U.C. Irvine – Daniela Bota
$8,000,000
INFR4-13597
UC San Diego Health CIRM Alpha Stem Cell Clinic
U.C. San Diego – Catriona Jamieson
$8,000,000
The Board also unanimously, and enthusiastically, approved the election of Maria Gonzalez Bonneville to be the next Vice Chair of the Board. Ms. Bonneville, the current Vice President of Public Outreach and Board Governance at CIRM, was nominated by all four constitutional officers: the Governor, the Lieutenant Governor, the Treasurer and the Controller.
In supporting the nomination, Board member Ysabel Duron said: “I don’t think we could do better than taking on Maria Gonzalez Bonneville as the Vice Chair. She is well educated as far as CIRM goes. She has a great track record; she is empathetic and caring and will be a good steward for the taxpayers to ensure the work we do serves them well.”
In her letter to the Board applying for the position, Ms. Bonneville said: “CIRM is a unique agency with a large board and a long history. With my institutional knowledge and my understanding of CIRM’s internal workings and processes, I can serve as a resource for the new Chair. I have worked hand-in-hand with both the Chair and Vice Chair in setting agendas, prioritizing work, driving policy, and advising accordingly. I have worked hard to build trusted relationships with all of you so that I could learn and understand what areas were of the most interest and where I could help shed light on those particular programs or initiatives. I have also worked closely with Maria Millan for the last decade, and greatly enjoy our working relationship. In short, I believe I provide a level of continuity and expertise that benefits the board and helps in times of transition.”
In accepting the position Ms. Bonneville said: “I am truly honored to be elected as the Vice Chair for the CIRM Board. I have been a part of CIRM for 11 years and am deeply committed to the mission and this new role gives me an opportunity to help support and advance that work at an exciting time in the Agency’s life. There are many challenges ahead of us but knowing the Board and the CIRM team I feel confident we will be able to meet them, and I look forward to helping us reach our goals.”
Ms. Bonneville will officially take office in January 2023.
The vote for the new Chair of CIRM will take place at the Board meeting on December 15th.
For many patients battling deadly diseases, getting access to a clinical trial can be life-saving, but it can also be very challenging. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved a concept plan to make it financially and logistically easier for patients to take part in CIRM-funded clinical trials.
The plan will create a Patient Support Program (PSP) to provide support to California patients being evaluated or enrolled in CIRM-supported clinical trials, with a particular emphasis on helping underserved populations.
“Helping scientists develop stem cell and gene therapies is just part of what we do at CIRM. If those clinical trials and resulting therapies are not accessible to the people of California, who are making all this possible, then we have not fulfilled our mission.” says Maria T. Millan, M.D., President and CEO of CIRM.
The Patient Support Plan will offer a range of services including:
Clinical trial navigation, directing patients to appropriate CIRM-supported clinical trials.
Logistical support for patients being evaluated or enrolled in clinical trials.
Financial support for under resourced and underserved populations in CIRM-supported clinical trials, including the CIRM Patient Assistance Fund (PAF). This support includes transportation/travel expenses, such as gasoline, tolls, parking, airfare, taxi, train, lodging, and meals during travel.
Providing nurse navigator support for the psychosocial, emotional, and practical needs of patients and their families.
The funds for the PSP are set aside under Proposition 14, the voter-approved initiative that re-funded CIRM in 2020. Under Prop 14 CIRM money that CIRM grantees earn from licensing, inventions or technologies is to be spent “offsetting the costs of providing treatments and cures arising from institute-funded research to California patients who have insufficient means to purchase such treatment or cure, including the reimbursement of patient-qualified costs for research participants.”
Currently, the CIRM Licensing Revenues and Royalties Fund has a balance of $15.6 million derived from royalty payments.
“The patient support program and financial resources will not only help patients in need, it will also help increase the likelihood that these clinical trials will succeed,” says Sean Turbeville, Ph.D., Vice President of Medical Affairs and Policy at CIRM. “We know cell and gene therapies can be particularly challenging for patients and their families. The financial challenges, the long-distance traveling, extended evaluation, and family commitments can make it difficult to enroll and retain patients. The aim of the PSP is to change that.”
The overall objective of this funding opportunity is to establish a statewide program that, over five years, is expected to support hundreds of patients in need as they participate in the growing number of CIRM-supported clinical trials. The program is expected to cost between $300,000 to $500,000 a year. That money will come from the Medical Affairs budget and not out of the patient assistance fund.
The first phase of the program will identify an organization, through a competitive process, that has the expertise to provide patient support services including:
Maintaining a call and support center.
Assessing patient eligibility for financial assistance.
Reporting to CIRM on patients needs and center performance
You can find more information about the Patient Support Program on our website here and here.
Clinical fellow Brian Shy talks with postdoctoral scholar Tori Yamamoto in the Marson Lab at Gladstone Institutes on June 8th, 2022. Photo courtesy Gladstone Institutes.
For years scientists have been touting the potential of CRISPR, a gene editing tool that allows you to target a specific mutation and either cut it out or replace it with the corrected form of the gene. But like all new tools it had its limitations. One important one was the difficult in delivering the corrected gene to mature cells in large numbers.
Scientists at the Gladstone Institutes and U.C. San Francisco say they think they have found a way around that. And the implications for using this technique to develop new therapies for deadly diseases are profound.
In the past scientists used inactivated viruses as a way to deliver corrected copies of the gene to patients. We have blogged about UCLA’s Dr. Don Kohn using this approach to treat children born with SCID, a deadly immune disorder. But that was both time consuming and expensive.
CRISPR, on the other hand, showed that it could be easier to use and less expensive. But getting it to produce enough cells for an effective therapy proved challenging.
The team at Gladstone and UCSF found a way around that by switching from using CRISPR to deliver a double-stranded DNA to correct the gene (which is toxic to cells in large quantities), and instead using CRISPR to deliver a single stranded DNA (you can read the full, very technical description of their approach in the study they published in the journal Nature Biotechnology).
Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and the senior author of the study, said this more than doubled the efficiency of the process. “One of our goals for many years has been to put lengthy DNA instructions into a targeted site in the genome in a way that doesn’t depend on viral vectors. This is a huge step toward the next generation of safe and effective cell therapies.”
It has another advantage too, according to Gladstone’s Dr. Jonathan Esensten, an author of the study. “This technology has the potential to make new cell and gene therapies faster, better, and less expensive.”
The team has already used this method to generate more than one billion CAR-T cells – specialized immune system cells that can target cancers such as multiple myeloma – and says it could also prove effective in targeting some rare genetic immune diseases.
The news that a stem cell transplant at City of Hope helped a man with HIV go into long-term remission made banner headlines around the world. As it should. It’s a huge achievement, particularly as the 66-year-old man had been living with HIV since 1988.
First the news. In addition to living with HIV the man was diagnosed with acute leukemia. Doctors at City of Hope found a donor who was not only a perfect match to help battle the patient’s leukemia, but the donor also had a rare genetic mutation that meant they were resistant to most strains of HIV.
In transplanting blood stem cells from the donor to the patient they were able to send both his leukemia and HIV into remission. The patient stopped taking all his antiretroviral medications 17 months ago and today has no detectable levels of HIV.
In a news release City of Hope hematologist Ahmed Aribi, M.D., said the patient didn’t experience any serious complications after the procedure.
“This patient had a high risk for relapsing from AML [acute myeloid leukemia], making his remission even more remarkable and highlighting how City of Hope provides excellent care treating complicated cases of AML and other blood cancers.”
It’s a remarkable achievement and is only the fifth time that a patient with both HIV and leukemia has been put into remission after a transplant from an HIV-resistant donor.
CIRM’s Contribution
So, what does that have to do with CIRM? Well, CIRM’s Alpha Clinics Network helped City of Hope get this case approved by an Institutional Review Board (IRB) and also helped in collecting and shipping the donor blood. In addition, part of the Alpha Clinics team at University of California San Diego helped with the reservoir analysis of blood and gut biopsies to check for any remaining signs of HIV.
It’s a reminder that this kind of achievement is a team effort and CIRM is very good at creating and supporting teams. The Alpha Clinics Network is a perfect example. We created it because there was a need for a network of world-class medical facilities with the experience and expertise to deliver a whole new kind of therapy. The Network has been remarkably successful in doing that with more than 200 clinical trials, taking care of more than 1,000 patients, and treating more than 40 different diseases.
This year our Board approved expanding the number of these clinics to better serve the people of California.
While the role of the Alpha Clinics Network in helping this one patient may seem relatively small, it was also an important one. And we are certainly not stopping here. We have invested more than $79 million in 19 different projects targeting HIV/AIDS, include four clinical trials.
We are in this for the long term and results like the man who had HIV and is now in remission are a sign we are heading in the right direction.
At the California Institute for Regenerative Medicine (CIRM) we are fortunate in having enough money to fund the most promising research to be tested in a clinical trial. Those are expensive projects, often costing tens of millions of dollars. But sometimes the projects that come to our Board start out years before in much more humble circumstances, raising money through patient advocates, tapping into the commitment and ingenuity of those affected by a disease, to help advance the search for a treatment.
That was definitely the case with a program the CIRM Board voted to approve yesterday, investing more than $11 million dollars to fund a Phase 2 clinical trial testing a cell therapy for dysphagia. That’s a debilitating condition that affects many people treated for head and neck cancer.
Patients with head and neck cancer often undergo surgery and/or radiation to remove the tumors. As a result, they may develop problems swallowing and this can lead to serious complications such as malnutrition, dehydration, social isolation, or a dependence on using a feeding tube. Patients may also inhale food or liquids into their lungs causing infections, pneumonia and death. The only effective therapy is a total laryngectomy where the larynx or voice box is removed, leaving the person unable to speak.
Dr. Peter Belafsky and his team at the University of California at Davis are developing a therapeutic approach using Autologous Muscle Derived Progenitor Cells (AMDC), cells derived from a biopsy of the patient’s own muscle, elsewhere in the body. Those AMDCs are injected into the tongue of the patient, where they fuse with existing muscle fibers to increase tongue strength and ability to swallow.
The $11,015,936 that Dr. Belafsky is getting from CIRM will enable them to test this approach in patients. But without grass roots support the program might never have made it this far.
Ed Steger is a long-term survivor of head and neck cancer, he’s also the President of the National Foundation of Swallowing Disorders (NFOSD). In 2007, after being treated for his cancer, Ed developed a severe swallowing disorder. It helped motivate him to push for better treatment options.
In 2013, a dozen swallowing disorder patients visited UC Davis to learn how stem cells might help people with dysphagia. (You can read about that visit here). Ed says: “We were beyond thrilled with the possibilities and drawing on patients and other UCD contacts our foundation raised enough funds to support a small UCD clinical trial under the guidance of Dr. Belafsky in mouse models that demonstrated these possibilities.”
A few years later that small funding by patients and their family members grew into a well-funded Phase I/II human clinical trial. Ed says the data that trial produced is helping advance the search for treatments.
“Skipping forward to the present, this has now blossomed into an additional $11 million grant, from CIRM, to continue the work that could be a game changer for millions of Americans who suffer annually from oral phase dysphagia. My hat is off to all those that have made this possible… the donors, patient advocates, and the dedicated committed researchers and physicians who are performing this promising and innovative research.”
Our hats are off to them too. Their efforts are making what once might have seemed impossible, a real possibility.
Almost every day, we hear new reports from the thousands of regenerative medicine clinical trials globally sponsored by hundreds of companies and academic researchers. The California Institute for Regenerative Medicine (CIRM) is a leader in this space supporting some of the most advanced cell and gene therapy clinic trials for a variety of unmet medical needs. With all this current activity, it’s easy to forget that there were only a handful of clinical trials going on just seven years ago.
A New System for Delivering Treatments
In 2015, CIRM’s leadership recognized that we were on the cusp of introducing an array of new regenerative medicine clinical trials. However, there was one big concern—the existing clinical delivery systems had limited experience and capacity for managing these new and comparatively complex clinical trials. Cell and gene therapy regenerative medicine treatments require new systems for manufacturing, processing, and delivering treatments to patients.
In anticipation of the need for clinical bandwidth to support clinical trials, CIRM funded a network of California medical centers to develop teams dedicated to supporting regenerative medicine clinical trials. This network was called the Alpha Clinics Network.
Since 2015, the Alpha Clinics Network has grown to include six academic medical centers in California. The Network has treated over a thousand patients in more than 100 clinical trials. CIRM frequently encounters companies and academic researchers that are specifically interested in bringing their research to California to be performed in the Alpha Clinics Network. These research sponsors cite expertise in manufacturing, process, delivery and regulatory compliance as the Networks value proposition. One sponsor summed it up by indicating there are “fewer protocol deviations (errors)” in the Alpha Clinics.
Expanding the Alpha Clinics Network
As we enter 2022 with CIRM’s new five year strategic plan, a major aim is to create a broad network of medical centers capable of supporting diverse patient participation in clinical trials.
As a first step in this effort, CIRM recently announced $80 million in funding to expand the Alpha Clinics Network. This funding is intended to expand both the scale and scope of the Network. This funding will allow the scale to grow from six medical center to up to ten. Scale is important because as the number of clinical trials grow, there needs to be increased coordination and sharing of the workload. Alpha Clinic sites already collaborate to conduct individual clinical trials, and an expanded network will enable a greater number of trials to occur simultaneously.
In addition, the Expansion Awards will enable the Network to expand the scope of its activities to address current needs of the field. These needs include new research platforms for conducting clinical trials. For example, sites are looking at integrating new types of genomic (DNA sequencing) tools to support improved diagnosis and treatment of patients.
Also, CIRM is committed to funding research to treat neurological diseases. We anticipate network sites will develop advanced systems for delivering treatments to patients and evaluating the effectiveness of these treatments. In addition, sites will be developing training programs to address the growing workforce needs of the field of regenerative medicine.
In 2015, CIRM invested in the Alpha Clinics Network which positioned California as a leader in supporting regenerative medicine clinical trials. In 2022, we will be expanding the Network with the aim of delivering transformative treatments to a diverse California and the world. The Network will fulfill this aim by expanding its reach in the state, developing advanced research planforms and technologies, and by training the next generations of researchers with the skills to deliver patient treatments.
Watch a recording of our recent Alpha Clinics concept plan webinar:
Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis
Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.
As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.
She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.
So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!
CIRM Bridges student discusses her poster presentation
At CIRM, the bread and butter of what we do is funding research and hopefully advancing therapies to patients. But the jam, that’s our education programs. Helping train the next generation of stem cell and gene therapy scientists is really inspiring. Watching these young students – and some are just high school juniors – come in and grasp the science and quickly become fluent in talking about it and creating their own experiments shows the future is in good hands.
Right now we fund several programs, such as our SPARK and Bridges internships, but they can’t cover everything, so last week the CIRM Board approved a new training program called COMPASS (Creating Opportunities through Mentorship and Partnership Across Stem Cell Science). The program will fill a critical need for skilled research practitioners who understand and contribute at all levels in the translation of science to medicine, from bench to bedside.
The objective of the COMPASS Training Program is to prepare a diverse group of undergraduate students for careers in regenerative medicine through the creation of novel recruitment and support mechanisms that identify and foster untapped talent within populations that are historically under-represented in the biomedical sciences. It will combine hands-on research with mentorship experiences to enhance transition of students to successful careers. A parallel objective is to foster greater awareness and appreciation of diversity, equity and inclusion in trainees, mentors, and other program participants
The CIRM Board approved investing $58.22 million for up to 20 applications for a five-year duration.
“This new program highlights our growing commitment to creating a diverse workforce, one that taps into communities that have been historically under-represented in the biomedical sciences,” says Dr. Maria T. Millan, President and CEO of CIRM. “The COVID19 pandemic made it clear that the benefits of scientific discovery are not always accessible to communities that most need them. CIRM is committed to tackling these challenges by creating a diverse and dedicated workforce that can meet the technical demands of taking novel treatment ideas and making them a reality.”
The Board also approved a new $80 million concept plan to expand the CIRM Alpha Stem Cell Clinic Network. The Network clinics are all in top California medical centers that have the experience and the expertise to deliver high-quality FDA-authorized stem cell clinical trials to patients.
There are currently five Alpha Clinics – UC San Diego; UCLA/UC Irvine; City of Hope; UCSF; UC Davis – and since 2015 they have hosted more than 105 clinical trials, enrolled more than 750 patients in these trials, and generated more than $95 million in industry contracts.
Each award will provide up to $8 million in funding over a five-year period. The clinics will have to include:
A demonstrated ability to offer stem cell and gene therapies to patients as part of a clinical trial.
Programs to help support the career development of doctors, nurses, researchers or other medical professionals essential for regenerative medicine clinical trials.
A commitment to data sharing and meeting CIRM’s requirements addressing issues of diversity, equity and inclusion and meeting the needs of California’s diverse patient population.
There is no benefit in helping create a miraculous new therapy that can cure people and save lives if no one except the super-rich can afford it. That’s why the California Institute for Regenerative Medicine (CIRM) has made creating a roadmap to help make new treatments both available and affordable for all Californians a central pillar of its new 5-year Strategic Plan.
New treatments based on novel new technologies often seem to come with a gob-smacking price tag. When Kymriah, a CAR-T cell cancer therapy, was approved it cost $475,000 for one treatment course. When the FDA approved Zolgensma to treat spinal muscular atrophy, a genetic disorder that causes muscle wasting and weakness, the cost was $2.1 million for one dose.
Part of the pricing is due to high manufacturing cost and the specialized resources needed to deliver the treatments. The treatments themselves are showing that they can be one-and-done options for patients, meaning just one treatment may be all they need to be cured. But even with all that innovation and promise the high price may impact access to patients in need.
At CIRM we believe that if California taxpayer money has helped researchers develop a new therapy, Californians should be able to get that therapy. To try and ensure they can we have created the Accessibility and Affordability Working Group (AAWG). The groups mission is to find a way to overcome the hurdles that stand between a patient and the treatment they need.
The AAWG will work with politicians and policy makers, researchers and regulators, insurance companies and patient advocate organizations to gather the data and information needed to make these therapies available and affordable. Dr. Le Ondra Clark Harvey, a CIRM Board member and mental health advocate, says the barriers we have to confront are not just financial, they are racial and ethnic too.
We have already created a unique model for delivering stem cell therapies to patients through our Alpha Stem Cell Clinic Network. We are now setting out to build on that with our commitment to creating Community Care Centers of Excellence. But having world-class clinics capable of delivering life-saving therapies is not enough. We also need to make sure that Californians who need these treatments can get them regardless of who they are or their ability to pay.
The Stem Cellar 