Apply Now for New Manufacturing Funding Opportunity

The California Institute for Regenerative Medicine (CIRM) has set goals through its five-year strategic plan to continue to deliver the full potential of regenerative medicine to the people of California and around the world. 

One of those goals is to overcome manufacturing hurdles for the delivery of regenerative medicine therapies by building a public-private manufacturing partnership network. 

This is essential because the field needs to create standardized manufacturing processes to transition from the production of smaller batches of therapies for use in clinical trials, to the larger batches required by full-scale commercialization. The manufacturing process for cell and gene therapies is more complex than for other biologics, so CIRM is committed to creating a network to overcome those challenges.

In working towards that goal, CIRM is pleased to announce a new funding opportunity within our Infrastructure Program, the INFR5 Cell and Gene Therapy Manufacturing Network (Phase 1) Awards.  
 
The California Cell and Gene Therapy Manufacturing Network aims to establish a statewide manufacturing network comprising academic process development and GMP manufacturing facilities as well as industry manufacturing partners that will: 

  1. Accelerate and de-risk pathways to commercialization for cell and gene therapies 
  1. Advance industry standards and incorporate quality-by-design in cell and gene therapy manufacturing, and 
  1. Build a diverse, highly skilled manufacturing workforce in California. 

CIRM will issue two phases of awards governed by two separate requests for applications (RFAs). This RFA describes the first phase of awards that will fund California academic cell and gene therapy GMP manufacturing facilities to make initial progress toward the three network goals (described above) at their individual facilities. 

To apply for this award, please visit our website to download the Program Announcement and access a link to the application.  

Update: If you’re interested in learning more about the INFR5 Phase 1 Awards, eligibility requirements, the application and review process, and more, the CIRM team hosted an informational webinar in November. Watch a video recording of the webinar here. The slide deck is available here.

The doctor who fights vision loss and wildfires

Dennis Clegg, UC Santa Barbara researcher

Doctor Dennis Clegg, a researcher and scientist at UC Santa Barbara, is fascinated by the eye. He thinks it’s one of the most beautiful objects in nature and wonders how something as complex and elegant developed and is able to connect with our brains to make vision possible. That’s why he has spent his career trying to understand that question and develop answers, to help reverse vision loss and blindness in people.

The good news is that Dennis and his colleagues have made encouraging progress in answering some of those questions. In one early-stage CIRM-funded clinical trial they were able to reverse the effects of macular degeneration, the leading cause of vision loss in the elderly.

So we sat down with Dennis to talk about his research, his love of dogs (he has six!) and his work as a volunteer firefighter. That’s all in the latest episode of our podcast, ‘Talking ‘Bout (re)Generation’.

Enjoy the show.

Dr. Deborah Deas and Ysabel Duron recognized for their contributions to advancing public health

Dr. Deborah Deas

The California Institute for Regenerative Medicine (CIRM) has two reasons to celebrate today.

Earlier this month, Dr. Deborah Deas was elected as a member of the National Academy of Medicine, or NAM. Membership in the academy is one of the highest national honors in health and medicine.

Dr. Deas is the vice chancellor of health sciences and the Mark and Pam Rubin Dean of the UCR School of Medicine, as well as a member of CIRM’s governing Board.

Amongst many other honors, Dr. Deas is recognized for being a national contributor to addressing health disparities through diversifying the physician workforce, especially around the shortage of Black males in medicine.

“I was ecstatic to learn that I was elected. It will allow me to have a greater voice at the national level in science as well as in diversity, equity, and inclusion. I’m also so pleased about what we are doing at CIRM, and this is such a great opportunity to not only represent myself but also the UC system as well as CIRM.”

Ysabel Duron (pictured on left) at While House Cancer Moonshot event.

Simultaneously, another Board member, founder and President of the Latino Cancer Institute Ysabel Duron was asked to join the American Cancer Society (ACS) National Breast Cancer Roundtable (NBCRT).

Last week, Ms. Duron attended the event at the white house with First Lady Dr. Jill Biden, where she announced the launch of NBCRT.

The ACS NBCRT is a national coalition working to accelerate progress across the breast cancer continuum through strategic partnerships to eliminate disparities and reduce mortality. The ACS NBCRT works to ensure all women have access to quality screening and treatment, including Black women and women in other historically excluded communities, to address the social and emotional needs of patients and their families.

“I feel both honored to join the ACS NBCRT and the weight of this responsibility and obligation to those who suffer and die from this horrific disease every day. I am also committed, during the critical next steps in determining initiatives to propose, to spotlight the gaps and needs in education, quality care and access to the most advanced diagnostics and treatment for Latina and other underserved populations.”

CIRM Board Approves Funding for New Clinical Trial Targeting Brain Tumors

The governing Board of the California Institute for Regenerative Medicine (CIRM) has awarded almost $12 million to carry out a clinical trial targeting brain tumors.

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:

ApplicationProgram TitleInstitution/Principal InvestigatorAmount awarded
INFR4-13579The Stanford Alpha Stem Cell ClinicStanford University – Matthew Porteus  $7,997,246  
INFR4-13581UCSF Alpha Stem Cell ClinicU.C. San Francisco – Mark Walters  $7,994,347  
INFR4-13586A 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    
INFR4-13587The 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
INFR4-13596Alpha Stem Cell Clinic for Northern and Central California  U.C. Davis – Mehrdad Abedi  $7,999,997  
INFR4-13685Expansion of the Alpha Stem Cell and Gene Therapy Clinic at UCLA  U.C. Los Angeles – Noah Federman  $8,000,000
INFR4-13878Alpha Clinic Network Expansion for Cell and Gene Therapies  University of Southern California – Thomas Buchanan  $7,999,983  
INFR4-13952A 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
INFR4-13597UC 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.

Developing a natural killer for cancer

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

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.”

Honor of a lifetime

Senator Art Torres (Retired), the Vice Chair of the CIRM Board, has had a pretty amazing life – you can read about some of his accomplishments here – and has received many honors. Last week he received one more. Art was given the Dolores Huerta Lifetime Achievement Award as part of the Latino Heritage Month Celebration.

This is no small honor. Dolores Huerta is one of the most influential labor and civil rights activists of the 20th century, so to receive this award is a testament to the dedication and commitment that Art has demonstrated over many years to health care, education, the environment and human rights among other things.

Fun fact. Dolores Huerta was the co-founder, along with Cesar Chavez, of the United Farm Workers’ Union (UFW), which was instrumental in getting better working conditions and wages for farm workers. One of Art’s first jobs, as a young lawyer, was working with the UFW and Dolores Huerta was his boss.

The award ceremony was something of a family affair as the MC for the event was Joaquin Torres, Art’s son and the current Assessor-Recorder for San Francisco. Dolores Huerta sent a video greeting, and San Francisco Mayor London Breed presented him with a Certificate of Honor, praising Art for:  “your advocacy and passion to secure critical funding for stem cell research, support our immigrant communities, and uplift our Latino residents has made you a true cornerstone of our city.”

How this scientist changed paths to become a stem cell researcher

Aaliyah Staples-West didn’t originally envision becoming a stem cell researcher. As a student at San Diego State University, she admits that she sometimes struggled with reading protocols or finishing experiments on time. She also was originally studying chemistry, a very distinct scientific field from regenerative medicine. 

But when she saw a post on Instagram about the California Institute for Regenerative Medicine (CIRM) Bridges to Stem Cell Research and Therapy internship program, she did a bit of research about it and ultimately stepped up to pursue the opportunity.   

“Everything I was looking for aligned with what I wanted to do,” she says. “I applied and I was greeted with open arms to an acceptance about a week later.” She even stayed in college for an extra semester so she could enroll in the CIRM internship program.

During the year-long internship—which took place at UC San Diego in the Sanford Consortium for Regenerative Medicine—Aaliyah studied and modeled a rare disease called Cockayne Syndrome B (CSB). CSB is a rare disease which causes short stature, premature aging, severe photosensitivity, and moderate to severe learning delay. 

In the lab, Aaliyah worked with stem cells to derive brain organoids, which are three-dimensional, organ-like clusters of cells. She also researched vascular endothelial cells, which form a single cell layer that lines all blood vessels. She tested and observed these to further understand the causes of CSB.  

Aaliyah also had opportunities to do work outside of the lab, traveling to various scientific conferences across the state to explain her work to other scientists.

She enjoyed sharing her findings, but Aaliyah says it was a challenge at first to learn all the complex science and terminology relating to stem cells. She overcame that obstacle by asking lots of questions and putting in extra effort to understanding the biology and reasoning behind her work.  

“I would write down all the terms my mentor would say that I didn’t understand and look them up,” she says. “I would even practice using them in a sentence. I made it very intentional that if I wanted to continue researching in this field I needed to be on the same page.”

Aaliyah and her Bridges cohort at the CIRM Bridges conference in San Diego.

Now that her internship is over, Aaliyah is much more confident and has learned various techniques to successfully complete research projects. She now works for biotechnology company Resilience as a research associate working with induced pluripotent stem cells (iPSCs) and hematopoietic stem cells. Though she originally intended to go to medical school, she is now looking into MD/PhD programs where she can apply all that she’s learned in her training and education.  

“I never thought I would have a love for stem cell research until participating in this program,” she says. “Stem cell research and regenerative medicine provide infinite opportunities for developing, understanding and potentially curing diseases. It’s important to continue this type of research to ensure science is quickly evolving and to make an impact on overall health.” 

To date, there are 1,663 Bridges alumni, and another 109 Bridges trainees are completing their internships in 2022.  Learn more about CIRM’s internship programs here

All photos courtesy of Sarah White/SDSU and Aaliyah Staples-West.

CIRM President & CEO Dr. Maria Millan recognized as one of the most influential women in Bay Area business

Dr. Maria Millan has been recognized by the San Francisco Business Times as one of the most influential women in Bay Area business for her work leading the California Institute for Regenerative Medicine (CIRM), California’s stem cell and regenerative medicine agency.  

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.  

Pioneering a new approach to HIV/AIDS

Dr. Steven Deeks. Photo courtesy UCSF

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.  

Today there are an estimated 38 million people living with HIV around the world. Every year some 650,000 people die from the disease.  

California researchers developing vaccine to curb the spread of Zika virus

Zika is caused by a virus that is mainly transmitted by infected female Aedes aegypti mosquitoes but also through sexual intercourse. People infected by Zika virus usually have mild symptoms that normally last for two to seven days and can include fever, skin rashes, conjunctivitis, muscle and joint pain, or headaches.

Zika also causes devastating congenital neurodefective disorders, most notably microcephaly, where a child’s head is much smaller than expected, in children born to infected mothers as well as neurological problems in those infected like Guillain-Barré syndrome.

To date, no vaccines or other treatments have been approved for Zika virus. Nor have investigations into other ways of fighting the virus led to clearly effective countermeasures. 

But there is good news. Researchers from the University of California, Los Angeles (UCLA) have developed a Zika vaccine technology that is both highly effective and safe in preclinical mouse models. The study—partially funded by the California Institute for Regenerative Medicine (CIRM)—found that in a pregnant mouse model, the vaccine prevented both the pregnant mothers and the developing fetuses from developing systemic infection. 

Dr. Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at the University of California, Los Angeles (UCLA) is a co-senior author of the study.

In engineering the vaccine, researchers deleted the part of the Zika genome that codes for the viral shell, the protective shell that a virus forms to evade the immune system. “This modification both stimulates an immunogenic reaction and prevents the virus from replicating and spreading from cell to cell,” said Vaithilingaraja Arumugaswami, D.V.M., Ph.D., Associate Professor of Molecular and Medical Pharmacology at UCLA.  

This is important progress because the average length of time between periods of extensive Zika viral spread is approximately 7 years. Given that the virus was last widespread in 2016, “it is only a matter of time before we start seeing the virus spread again,” said Kouki Morizono, M.D., Ph.D., Associate Professor of Medicine at UCLA and co-senior author of this study. 

“The ongoing COVID-19 pandemic has shown us the power of a strong pandemic preparedness plan and clear communication about prevention methods – all culminating in the rapid rollout of safe and reliable vaccines. Our research is a crucial first step in developing an effective vaccination program that could curb the spread of Zika virus and prevent large-scale spread from occurring,” said Arumugaswami. 

This research is published in Microbiology Spectrum,  a journal of the American Society for Microbiology.