We at the California Institute for Regenerative Medicine have a lot to be thankful for this Thanksgiving. We get to work with some extraordinary colleagues, we get to know some remarkable patient advocates who are pioneers in volunteering for stem cell and gene therapies, and we have a front row seat in a movement that is changing the face of medicine.
We also get to work with some brilliant scientists and help support their research. As if we needed any reminders of how important that funding is, we thought we would share this video with you. It’s from the talented post docs and researchers at the University of California San Diego. It’s a delightful parody of the Cyndi Lauper classic “Girls Just Wanna Have Fun”. Only in this case it’s “Nerds Just Wanna Have Funds.”
Let’s back up a little. Children born with SCID have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life. Several of the approaches CIRM has funded use the child’s own blood stem cells to help fix the problem. But at Jasper Therapeutics they are using another approach. They use a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s own blood supply with one that is free of the SCID mutation, which helps restore their immune system.
However, there’s a problem. Most bone marrow transplants use chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. It can be effective, but it is also toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.
To get around that problem Jasper Therapeutics is using an antibody called JSP191 – developed with CIRM funding – that directs the patient’s own immune cells to kill diseased blood stem cells, creating room to transplant new, healthy cells. To date the therapy has already been tested in 16 SCID patients.
In addition to treating 16 patients treated without any apparent problems, Jasper has also been granted Fast Track Designation by the US Food and Drug Administration. This can help speed up the review of treatments that target serious unmet conditions. They’ve also been granted both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.
In a news release, Ronald Martell, President and CEO of Jasper Therapeutics said:
“The FDA’s Fast Track designation granted for JSP191 in Severe Combined Immunodeficiency (SCID) reinforces the large unmet medical need for patients with this serious disease. Along with its previous designations of Orphan and Rare Pediatric Disease for JSP191, the FDA’s Fast Track recognizes JSP191’s potential role in improving clinical outcomes for SCID patients, many of whom are too fragile to tolerate the toxic chemotherapy doses typically used in a transplant.”
The headline in the journal Nature was intended to grab attention and it definitely did that. It read: ‘The scandal of researchers paid less than a living wage’ The rest of the article built on that saying “The cost-of-living crisis is a fundamental threat for PhD scholars and early-career researchers. They need to be paid properly.”
So, just how poorly are these researchers – PhD candidates and postdoctoral students – paid? Well, according to one survey salaries for PhD students in the biological sciences are below the cost of living at almost every institution in the United States. And imagine trying to live on a sub-standard income in a state as expensive as California?
The outrage is fueled by a survey of more than 3,200 students, three quarters of whom are PhD candidates. Around 85% of the students said inflation is making things even worse and almost half said it was making it hard to complete their courses.
The situation isn’t any better in other countries. In the UK, PhD students often get the equivalent of just $20,400, and that’s after getting a recent big boost of more than $2,000 per year. It’s no wonder English students organized protests calling for better funding. Students in Ireland also staged protests, saying the money they get simply isn’t enough.
The Nature Editorial said this isn’t just a matter of inconvenience for the students, it’s a threat to the future of science: “If students don’t have the resources to support themselves, they can’t put their full efforts into their training and development. And if their stipends aren’t keeping pace with rising rents and the cost of groceries and fuel, any gaps will only grow with time — with devastating results for the ability of research to attract the best talent.”
That’s one of the reasons the California Institute for Regenerative Medicine (CIRM) tries to make sure all the students in its internship programs have enough money to live on. We know it’s hard to focus on work if you are hungry or worried that you don’t have enough money to pay your bills.
When our Board approved a new internship program, called COMPASS (Creating Opportunities through Mentorship and Partnership Across Stem Cell Science) they made sure that enough money was included to cover students living expenses, course fees and even travel to scientific conferences. The Board allocated more than $58,000 a year to support each students, many of whom will come from poor or low-income communities and might not otherwise be able to afford to stay in school.
For our Bridges students, many of whom are also from low-income communities or are the first in their family to attend college, the Board allocated each one around $72,000 worth of support per year.
We know that the future of regenerative medicine in California depends on having a skilled, well-trained, diverse workforce. That doesn’t just mean PhDs doing the research, it also means the technicians and support staff that can help with manufacturing etc. Without a living wage that makes this possible many students will drop out and the field as a whole will struggle. Those most affected will be students from poor backgrounds or from disadvantaged and historically marginalized communities.
We need to support these students in every way we can. If we don’t provide enough financial support for these students to succeed, the field as a whole will be a lot poorer.
It’s always nice to be told you are doing a good job. It’s even nicer when it’s unexpected. That’s certainly the case when we, the Communications Team at the California Institute for Regenerative Medicine, found out we’d been named as a finalist for the Patient Advocacy Award (non-profit category) as part of the Phacilitate Advanced Therapies Awards.
To be honest, we didn’t even know we’d been nominated. But who cares. We are now in the final. And we are in good company. Our friends at Americans for Cures, were also nominated. They are advocates for stem cell research in California and were hugely instrumental in getting Proposition 14 passed in 2020, that’s the voter initiative that refunded CIRM with $5.5 billion.
While we may focus on different areas we all share a common goal, a desire to ensure that the voice of the patient is front and center in all that we do. At CIRM we have patient advocates on our Board and on the panel of experts who review applications for our funding. We have patient advocates helping guide the clinical trials we fund. And now, as we expand our efforts to reach out in every community in California, we have patients and patient advocates guiding that work as well.
We do this work because it’s important and because, without the support of the patient advocacy community, we wouldn’t be here.
It’s an old cliché that when you are in this position you say, “it’s an honor just to be nominated.” But in this case, it’s true.
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:
The Stanford Alpha Stem Cell Clinic
Stanford University – Matthew Porteus
UCSF Alpha Stem Cell Clinic
U.C. San Francisco – Mark Walters
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
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
Alpha Stem Cell Clinic for Northern and Central California
U.C. Davis – Mehrdad Abedi
Expansion of the Alpha Stem Cell and Gene Therapy Clinic at UCLA
U.C. Los Angeles – Noah Federman
Alpha Clinic Network Expansion for Cell and Gene Therapies
University of Southern California – Thomas Buchanan
A hub and spoke community model to equitably deliver regenerative medicine therapies to diverse populations across four California counties
U.C. Irvine – Daniela Bota
UC San Diego Health CIRM Alpha Stem Cell Clinic
U.C. San Diego – Catriona Jamieson
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.
When Lili Yang was studying for her PhD she approached her mentor, the Nobel Laureate Dr. David Baltimore, and told him she was thinking about writing her thesis on a combination of gene therapy, immunotherapy and stem cell therapy. She says he looked at her and told her that all three of those approaches had a bad reputation because of so many past failures. He asked her, “Are you sure?” She was.
Fast forward 20 years and Dr. Yang and her team at UCLA have developed stem cell-engineered invariant Natural Killer T (iNKT) cells, a kind of specialized immune system cell, that has the ability to attack and kill a broad range of cancerous cells, while leaving the body’s healthy tissues unharmed.
Thanks to several CIRM grants, Dr. Yang has developed a platform that can use healthy donor blood stem cells to produce clinical scalable “off-the-shelf” iNKT cells. That has led to the creation of Appia Bio, a start-up company, and talks with the FDA about testing a series of iNKT cell products in clinical trials.
Besides developing cell products targeting the more established blood cancer disease indications, Dr. Yang is most excited about using the same platform to generate off-the-shelf iNKT cell products that could target solid tumor cancers that comprise over 90% of the total cancer cases, such as breast, ovarian, prostate, lung, liver, and colon cancers.
“I have this dream that cell therapy can become off-the-shelf, and how this would really help all cancer patients in need. The current cancer cell therapy requires treating patients one-by-one, resulting in a steep price that is hard to afford ($300,000-$500,000 per patient per treatment) and a complex therapy delivery logistics that is challenging to fulfill (coordination of hospitalization, blood collection, cell manufacturing and infusion for each patient). Not everyone lives near a hospital capable of handling such a personalized therapy or can afford such a steep price. If we can make this therapy with centralized manufacturing, pre-quality controlled and ready for wide use then we don’t need to worry about the gender or age or location of the patient. For off-the-shelf therapy, price is also expected to drop down significantly- this will eventually be ready for everyone everywhere.”
Under her leadership, CIRM has generated a robust and growing portfolio as a patient-centric funder, partner, accelerator, and de-risker for over 1,000 projects in basic, translational, and clinical research, as well as infrastructure and education programs.
In addition to highlighting her achievements at CIRM, Dr. Millan also shared some of her personal background with the publication.
“I immigrated to the U.S. from the Philippines at 6 years old with my younger siblings one year after my mother, accompanied by my father, was recruited as a nurse to New York City,” she said. “I honed down my English watching ‘Sesame Street’ and the ‘Electric Company.’”
When asked about the biggest obstacle facing women leaders, Dr. Millan said, “Work-life balance, learning that ‘good’ is enough in certain circumstances to achieve ‘great,’ and embracing what makes us unique — our experiences as women and as mothers and to leveraging those skills to leadership roles.”
Congratulations to Dr. Millan and this year’s winners! To see the full list of award recipients, click here.
I’ve always been impressed by the willingness of individuals to step forward and volunteer for a clinical trial. Even more so when they are the first person ever to test a first-in-human therapy. They really are pioneers in helping advance a whole new approach to treating disease.
That’s certainly the case for the first individual treated in a CIRM-funded clinical trial to develop a functional cure for HIV/AIDS. Caring Cross announced recently that they have dosed the first patient in the trial testing their anti-HIV duoCAR-T cell therapy.
The trial is being led by UC San Francisco’s Dr. Steven Deeks and UC Davis’ Dr. Mehrdad Abedi. Their approach involves taking a patient’s own blood and extracting T cells, a type of immune cell. The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells. The modified T cells are then reintroduced back into the patient.
The goal of this one-time therapy is to act as a long-term control of HIV with patients no longer needing to take anti-HIV medications. If it is successful it would be, in effect, a form of functional HIV cure.
This first phase involves giving different patients different levels of the duoCAR-T therapy to determine the best dose, and to make sure it is safe and doesn’t cause any negative side effects.
This is obviously just the first step in a long process, but it’s an important first step and certainly one worth marking. As Dr. Deeks said in the news release, “We have reached an important milestone with the dosing of the first participant in the Phase 1/2a clinical trial evaluating a potentially groundbreaking anti-HIV duoCAR-T cell therapy. Our primary goal for this clinical trial is to establish the safety of this promising therapeutic approach.”
Dr. Abedi, echoed that saying. “The first participant was dosed with anti-HIV duoCAR-T cells at the UC Davis medical center in mid-August. There were no adverse events observed that were related to the product and the participant is doing fine.”
This approach carries a lot of significance not just for people with HIV in the US, but also globally. If successful it could help address the needs of people who are not able to access antiretroviral therapies or for whom those medications are no longer effective.
Projects funded through the Foundation Awards should propose impactful or innovative research that culminates in a discovery or technology that would:
Advance our understanding of the biology of stem or progenitor cells that is relevant to human biology and disease; or
Advance the application of genetic research that is relevant to human biology and disease and pertains to stem cells or regenerative medicine; or
Advance the development or use of human stem cells as tools for biomedical innovation; or
Lead to the greater applicability of regenerative medicine discoveries to communities representing the full spectrum of diversity.
CIRM’s goal is that the outcomes of the projects derived from this opportunity will ultimately create new avenues and provide a rigorous foundation for translational and clinical development work.
Since Proposition 14 dedicates more than a quarter of funds to support research and development of treatments for diseases and conditions of the brain and central nervous system (CNS), CIRM encourages the submission of proposals focused on increasing our understanding of the fundamental biology of CNS disorders.
The CIRM Science team recently hosted a webinar addressing DISC0 eligibility requirements, the application and review process, and how this program fits into CIRM’s overall Strategic Plan and Mission. The webinar includes a half-hour presentation by CIRM staff followed by a half-hour for Q&A. You can view the webinar below or direct any questions about the program and applications to email@example.com.
Spina bifida is a birth defect that occurs when the spine and spinal cord don’t form properly and can result in life-long walking and mobility problems for the child, even paralysis.
Now, UC Davis has released more details about the clinical trial and the babies born after receiving the world’s first spina bifida treatment combining surgery with stem cells. The story was featured in BBC News and The Sacramento Bee.
The first phase of the trial is funded by a $9 million grant from the California Institute for Regenerative Medicine.
The one-of-a-kind treatment, delivered while a fetus is still developing in the mother’s womb, could improve outcomes for children with this birth defect.
A Decade’s Work
“I’ve been working toward this day for almost 25 years now,” said Dr. Diana Farmer, the world’s first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.
In previous clinical trial, Farmer had helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.
Farmer recruited bioengineer Dr. Aijun Wang to help take that work to the next level. Together, they researched and tested ways to use stem cells and bioengineering to advance the effectiveness and outcomes of the surgery.
Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida.
Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a “patch,” helped lambs with spina bifida walk without noticeable disability. When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.
The CuRe Trial
When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial, as the clinical trial is known.
Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.
After screenings, MRI scans and interviews, Emily received the news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.
Farmer and Wang’s team manufactured clinical grade stem cells—mesenchymal stem cells—from placental tissue in the UC Davis Health’s CIRM-funded Institute for Regenerative Cures. The lab is a Good Manufacturing Practice (GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emily’s fetal surgery.
During Emily’s historic procedure, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect.
Then, the stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate. The team declared the first-of-its-kind surgery a success.
On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via C-section.
For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie had remained untreated, she was expected to be born with leg paralysis.
“It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, ‘Oh my God, I think she’s wiggling her toes!’” said Farmer. “It was amazing. We kept saying, ‘Am I seeing that? Is that real?’”
Both mom and baby are at home and in good health. Robbie just celebrated her first birthday.
The CuRe team is cautious about drawing conclusions and says a lot is still to be learned during this safety phase of the trial. The team will continue to monitor Robbie and the other babies in the trial until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training.
“This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come,” Emily said. “We are honored to be part of history in the making.”
Read the official release from UC Davis Health here.