Her list of achievements continues to grow, as President Biden has appointed Duron to National Cancer Advisory Board (NCAB), which plays an important role in setting the course for the national cancer research program.
The National Cancer Advisory Board will complement the Cancer Moonshot, which President Biden reignited a year ago to invest in research and development that will help advance breakthroughs to prevent, detect and treat diseases like cancer.
“As a Latina, and a long-time patient and community advocate, it humbles me to join this roster of stellar new appointees,” Duron said. “I look forward to the challenge of amplifying the voices of racial and ethnic communities and other vulnerable populations.”
Duron came into the cancer space after her own bout with Hodgkins Lymphoma in 1999. She covered her own cancer battle using her reporting skills to raise awareness about the disease.
Over time, she turned a spotlight on the many disparities—lack of access, income inequality, language barriers, among other social determinants on health—that has exacerbated the disproportionate burden of cancer in Latino communities.
In 2017, Ms. Duron founded The Latino Cancer Institute (TLCI), a nationwide network dedicated to developing and sharing best practice programs to enhance the work of Latino community service agencies, to provide collaboration with the global cancer research community, and drive policy to solve the issues and burden of Latinx/Hispanic cancer.
The California Institute for Regenerative Medicine (CIRM) is investing $4 million to support Dr. William Murphy and UC Davis researchers to develop and test a chimeric antigen receptor (CAR) T-cell therapy to treat various B-cell malignancies, ranging from lymphomas to leukemias.
In this Q&A—courtesy of UC Davis Health—Dr. Murphy discusses the importance of T-cell therapy and its implications for developing cancer treatments. His work is a collaboration between CIRM, the nonprofit organization Caring Cross, and UC Davis Health.
What are B-cell malignancies?
B-cells are a type of white blood cells that make antibodies. They are key to the body’s immune system. When healthy B-cells change into fast-growing cancer cells that don’t die, they cause B-cell malignancies.
This can affect people at different ages. They may show up in children as B-cell acute lymphoblastic leukemia (B-ALL), an aggressive blood and bone marrow cancer. In adults, they make up about 85% of non-Hodgkin lymphoma (NHL), a cancer that starts in B lymphocytes. In the elderly, B-cell malignancies may come as multiple myeloma, a cancer of the plasma cells.
There are different lines of treatments for B-cell lymphoma and leukemia, including immunotherapy using chimeric antigen receptor (CAR) T cells. These cells have revolutionized cancer treatment since they have been shown to work, and cure, when nothing else can.
What is chimeric antigen receptor (CAR) T-cell therapy?
Chimeric antigen receptor (CAR) T-cell therapy uses the body’s own defenses to fight disease. It is a new and exciting form of immunotherapy that works by modifying the receptors of immune cells (T cells) involving antibodies to target specific cancers, such as leukemias and lymphomas.
CAR T cells are being used to treat some blood cancers with long-term success. The U.S. Food and Drug Administration (FDA) first approved CAR T-cell therapy in 2017. Their use is growing rapidly and being applied to other tumor types. Yet, this therapy is extremely expensive, even with insurance. It’s also a very intensive procedure and it takes time to generate the CAR T cells from the patient.
While it could be considered a game changer, one of the issues with this therapy is the case relapse rate. The big holy grail in cancer therapy is how to prevent tumors from evading or escaping the immune attack. Around 60% of patients who get CAR therapy see their cancer return. If we can get the relapse rate down to negligible, that would be a tremendous advance.
How do you intend to use CAR products to reduce cancer relapse?
In CAR therapy, we take the immune T cells from a patient and use gene therapy to give a new receptor to signal and direct the T cell. The receptor usually has an antibody that recognizes a particular tumor antigen. Current FDA-approved CAR T therapies only target one tumor antigen.
CARs have had tremendous success. However, there is significant patient relapse because the tumor adapts and may lose that one antigen that we are targeting, allowing it to escape the treatment. Our strategy is to target multiple antigens to reduce the potential for relapse since the tumor cannot adapt that quickly.
We are also proposing a novel vector that will carry a CAR product, known as DuoCAR, that targets three antigens at the same time. As long as the tumor has one of the three antigens, then there’s little chance for the tumor to escape all three antibodies. This is similar to when you think about HIV treatment with the triple-drug therapy, where one alone is not sufficient.
The hope is that the 60 to 70% of the population who would have relapsed if they had the original CAR T cell treatment, would have a home run with our kind of treatment or product.
So, is this treatment for cancer patients who have relapsed?
We see this product as a new frontline therapy and not just for patients who relapse. What the patient has to go through in order for CAR T therapy to work is very strenuous. So, yes, if there are relapsed patients, they can be given DuoCAR, but we’re also hoping this will become the new standard of care, replacing the other CARs in the future for everyone.
Adult acute myelogenous leukemia—also known as acute myeloid leukemia (AML)—is a blood cancer in which the bone marrow makes a large number of abnormal blood cells.
About 20,000 new cases of AML are diagnosed each year in the US with a 5-year survival rate of around 29%. In 2022, there were nearly 12,000 deathsfrom AML. Many AML patients—a majority of which are over 60 years old—relapse after treatment. Blood stem cell transplant can be curative, but many older patients do not qualify, showing that there is a significant unmet medical need in treating AML.
To develop the cancer vaccine, Dr. Gaensler and her team will engineer the patient’s blood stem cells to maximize stimulation of leukemia-specific killing activity and reintroduce engineered cells back to the patient to target and kill residual leukemia stem cells.
This approach holds the potential for long-term effectiveness as it targets both AML blasts and leukemic stem cells that are often the source of relapse.
This award is a continuation of a previous CIRM grantthat will support the manufacture of the vaccine and the completion of late-stage testing and preparation needed to apply to the US Food and Drug Administration (FDA) for permission to begin a clinical trial.
Blood stem cell transplantation following high dose chemotherapy is standard of care and potentially curative for aggressive forms of lymphoma. However, this treatment regimen is limited by severe toxicity and life-threatening complications due to delayed recovery of the blood system and vascular related damage of multiple organs.
This brings the number of clinical trials funded by CIRM to 86.
The Board awarded $15,000,000 to Dr. Paul Finnegan and Angiocrine Bioscience to test AB-205, human endothelial cells engineered to express a pro-survival factor.
Prior data suggest that, in the setting of chemotherapy and stem cell transplantation, AB-205 cell therapy can accelerate the recovery of the blood system and protects from toxicity by enhancing the recovery from vascular damage. AB-205 is being studied in a Phase 3 trial in adults with lymphoma undergoing high-dose chemotherapy and autologous blood stem cell transplant.
“If successful, this approach can overcome hurdles to the success of chemotherapy and blood stem cell transplantation for the treatment of advanced blood cancer,” says Dr. Maria T. Millan, President and CEO of CIRM. “This Phase 3 trial is the culmination of preclinical research and the initial clinical trial previously funded by CIRM.”
Lymphoma is the most common blood cancer and one of the most common cancers in the United States, accounting for about 4% of all cancers according to the American Cancer Society and the 6th most commonly diagnosed cancer among men and women in California. It is estimated that there will be 89,010 new cases of lymphoma and 21,170 lymphoma related deaths in the US in 2022 alone. In California, it is estimated that there will be over 9,250 new cases of lymphoma with over 2,100 deaths.
“Angiocrine Bioscience is honored to be awarded this grant from CIRM to support our AB-205 Phase 3 trial,” commented Angiocrine CEO Dr. Paul Finnegan. “CIRM has been an instrumental partner in our development of AB-205, a novel therapeutic that acts on the patients’ endogenous stem cell niches. The grant award will considerably aid in our effort to bring forth a solution to the unmet need of transplant-related complications.”
Every year California performs around 100 kidney transplants in children but, on average, around 50 of these patients will have their body reject the transplant. These children then have to undergo regular dialysis while waiting for a new organ. Even the successful transplants require a lifetime of immunosuppression medications. These medications can prevent rejection but they also increase the risk of infection, gastrointestinal disease, pancreatitis and cancer.
Dr. Alice Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that uses combined blood stem cell (HSC) and kidney transplantation with the goal to improve outcomes with kidney transplantation in children. This approach seeks to improve on the blood stem cell preparation through an immune-based purification process.
In this approach, the donor HSC are transplanted into the patient in order to prepare for the acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney providing the opportunity to avoid long-term need for medications that suppress the immune system.
Pre-clinical data support the idea that this approach could enable the patient to stop taking any immunosuppression medications within 90 days of the surgery.
Dr. Maria T. Millan, President and CEO of CIRM, a former pediatric transplant surgeon and tolerance researcher states that “developing a way to ensure long-term success of organ transplantation by averting immune rejection while avoiding the side-effects of life-long immunosuppression medications would greatly benefit these children.”
The CIRM Board also awarded $7,141,843 to Dr. Ivan Kingand Tachyon Therapeutics, Inc to test a drug showing promise in blocking the proliferation of cancer stem cells in solid tumors such as colorectal and gastrointestinal cancer.
Patients with late-stage colorectal cancer are typically given chemotherapy to help stop or slow down the progression of the disease. However, even with this intervention survival rates are low, usually not more than two years.
Tachyon’s medication, calledTACH101, is intended to target colorectal cancer (CRC) stem cells as well as the bulk tumor by blocking an enzyme called KDM4, which cancer stem cells need to grow and proliferate.
In the first phase of this trial Dr. King and his team will recruit patients with advanced or metastatic solid tumors to assess the safety of TACH101, and determine what is the safest maximum dose. In the second phase of the trial, patients with gastrointestinal tumors and colorectal cancer will be treated using the dose determined in the first phase, to determine how well the tumors respond to treatment.
The CIRM Board also awarded $5,999,919 to Dr. Natalia Gomez-Ospina and her team at Stanford University for a late-stage preclinical program targeting Severe Mucopolysaccharidosis type 1, also known as Hurler syndrome. This is an inherited condition caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs. There is no effective treatment and life expectancy for many of these children is only around ten years.
Dr. Gomez-Ospina will use the patient’s own blood stem cells that have been genetically edited to restore the missing enzyme. The goal of this preclinical program is to show the team can manufacture the needed cells, to complete safety studies and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.
Finally the Board awarded $20,401,260 to five programs as part of its Translational program. The goal of the Translational program is to support promising stem cell-based or gene projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use. Those can include therapeutic candidates, diagnostic methods or devices and novel tools that address critical bottlenecks in research.
The successful applicants are:
PRINCIPAL INVESTIGATOR – INSTITUTION
Cell Villages and Clinical Trial in a Dish with Pooled iPSC-CMs for Drug Discovery
Nikesh Kotecha — Greenstone Biosciences
Specific Targeting Hypoxia Metastatic Breast Tumor with Allogeneic Off-the-Shelf Anti-EGFR CAR NK Cells Expressing an ODD domain of HIF-1α
Jianhua Yu — Beckman Research Institute of City of Hope
CRISPR/Cas9-mediated gene editing of Hematopoietic stem and progenitor cells for Friedreich’s ataxia
Stephanie Cherqui — University of California, San Diego
Development of a Gene Therapy for the Treatment of Pitt Hopkins Syndrome (PHS) – Translating from Animal Proof of Concept to Support Pre-IND Meeting
Allyson Berent — Mahzi Therapeutics
Overcoming resistance to standard CD19-targeted CAR T using a novel triple antigen targeted vector
William J Murphy — University of California, Davis
In a new study, researchers from UC San Francisco and Vanderbilt University Medical Center have identified specific immune cells that cause a potentially lethal heart inflammation -called myocarditis- in a small fraction of patients treated with powerful cancer immunotherapy drugs.
Myocarditis is inflammation of the heart muscle. It can cause chest pain, shortness of breath, and rapid or irregular heart rhythms. Myocarditis can weaken the heart and its electrical system. As a result, the heart’s ability to pump blood declines. In severe cases, myocarditis causes clots and may lead to stroke, heart attack, heart failure and even death.
The form of myocarditis the researchers studied is a rare but deadly side effect of cancer immunotherapy drugs called immune checkpoint inhibitors (ICIs).
ICI is a type of therapy method that can improve the anti-tumor immune response by regulating the activity of T cells. ICI treatment has proven lifesaving for many cancer patients and fewer than one percent of patients who receive ICI develop myocarditis.
Using genetically altered mice to mimic human ICI-caused myocarditis in the new study, the researchers found an excess of immune system cells called CD8 T lymphocytes in the inflamed heart tissue of mice with myocarditis.
“We earlier observed many T cells in patients who had died, but in the mice we performed several key experiments to show that the T lymphocytes really are drivers of the disease process, and not merely innocent bystanders,” Moslehi said. “There are therapeutic implications to this study.”
The results of the study led the researchers to conclude that activation of CD8 T cells is necessary to trigger myocarditis in ICI-treated cancer patients and therefore immunosuppressive therapies that affect CD8 T cells might play a beneficial role.
Their new findings already have led them to begin investigating better ways to prevent and treat myocarditis. The research team already has reported a case study in which they used Abatacept, a rheumatoid arthritis drug that suppresses the activation of CD8 T cells, to successfully treat myocarditis in a cancer patient.
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.”
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.”
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.”
Our 2021-22 Annual Report is now online. It’s filled with information about the work we have done over the last year (we are on a fiscal calendar year from July 1 – June 30), the people who have helped us do that work, and some of the people who have benefited from that work. One of those is Regina Karchner.
Regina Karchner says she feels as if she’s been a patient advocate for people with brain cancer almost from birth. When she was three, her father died of a brain tumor. When she was 16 Regina was diagnosed with brain cancer. While she was in the hospital she heard about the Children’s Brain Tumor Foundation (CBTF) and as soon as she was able she became a volunteer with the organization. Today she is a social work regional coordinator at CBTF.
She says that as an advocate she feels she has a responsibility to help families deal with devastating news, to talk about death, and how to cope with the emotional trauma of it. She also advocates on behalf of survivors, like herself.
“I am just such an advocate for the need for long term programming for brain cancer survivors, because it’s so different from other cancers. The emotional, cognitive and physical impacts of brain tumors are dramatic, that’s even if the individuals survive.
“We are working with people in their 40’s who were the first group of childhood survivors and there’s nowhere to go that matches their needs, they can’t function enough to live independently and work full time. It’s a big problem in the medical world and even in schools, they don’t understand brain tumors, they don’t see it as a traumatic brain injury which it is and even the most well-intended schools don’t really know what to do or handle the patients.”
“We found that survivors with better social skills have a better quality of life, so we are now trying to focus on kids in elementary school, giving them the social skills they need to survive and that are hard to catch up on later in life. They can get math or history or other subjects anytime, but the social skills are essential”
Regina also serves on a CIRM Clinical Advisory Panel or CAP for a clinical trial for children with brain cancer. She says having the patient advocate at the table is vital to the success of the trial. “I help the researchers understand the needs of the patient, even understand why families don’t enroll in trials. 80% of families who have kids with brain tumors are on Medicaid so it’s a select group of people who can afford to be in these trials. Letting the researchers know that and coming up with ways to help them is so important.”
She says it’s challenging work, but also very rewarding. “It feels wonderful to help families in a time of need. I feel I grow as a person and as a parent, I have learnt so much that helps me in my personal life and being grateful for having a healthy family and being a healthy survivor myself.”