Celebrating Stem Cell Awareness Day

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The second Wednesday in October is celebrated as Stem Cell Awareness Day. It’s an event that CIRM has been part of since then Governor Arnold Schwarzenegger launched it back in 2008 saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.”

In the past we would have helped coordinate presentations by scientists in schools and participated in public events. COVID of course has changed all that. So, this year, to help mark the occasion we asked some people who have been in the forefront of making Governor Schwarzenegger’s statement come true, to share their thoughts and feelings about the day. Here’s what they had to say.

What do you think is the biggest achievement so far in stem cell research?

Dr. Jan Nolta

Jan Nolta, PhD., Director of the Stem Cell Program at UC Davis School of Medicine, and directs the new Institute for Regenerative Cures. “The work of Don Kohn and his UCLA colleagues and team members throughout the years- developing stem cell gene therapy cures for over 50 children with Bubble baby disease. I was very fortunate to work with Don for the first 15 years of my career and know that development of these cures was guided by his passion to help his patients.

Dr. Clive Svendsen

Clive Svendsen, PhD. Director, Board of Governors Regenerative Medicine Institute at Cedars-Sinai: “Without a doubt the discovery of how to make human iPSCs by Shinya Yamanaka and Jamie Thomson.”

When people ask you what kind of impact CIRM and stem cell research has had on your life what do you say?

Ronnie and his parents celebrating his 1st birthday. (Photo courtesy of Pawash Priyank)

Pawash Priyank and Upasana Thakur, parents of Ronnie, who was born with a life-threatening immune disorder but is thriving today thanks to a CIRM-funded clinical trial at UC San Francisco. “This is beyond just a few words and sentences but we will give it a shot. We are living happily today seeing Ronnie explore the world day by day, and this is only because of what CIRM does every day and what Stem cell research has done to humanity. Researchers and scientists come up with innovative ideas almost every day around the globe but unless those ideas are funded or brought to implementation in any manner, they are just in the minds of those researchers and would never be useful for humanity in any manner. CIRM has been that source to bring those ideas to the table, provide facilities and mechanisms to get those actually implemented which eventually makes babies like Ronnie survive and see the world. That’s the impact CIRM has. We have witnessed and heard several good arguments back in India in several forums which could make difference in the world in different sectors of lives but those ideas never come to light because of the lack of organizations like CIRM, lack of interest from people running the government. An organization like CIRM and the interest of the government to fund them with an interest in science and technology actually changes the lives of people when some of those ideas come to see the light of real implementation. 

What are your biggest hopes for the future at UC Davis?

Jan Nolta, PhD: “The future of stem cell and gene therapy research is very bright at UC Davis, thanks to CIRM and our outstanding leadership. We currently have 48 clinical trials ongoing in this field, with over 20 in the pipeline, and are developing a new education and technology complex, Aggie Square, next to the Institute for Regenerative Cures, where our program is housed. We are committed to our very diverse patient population throughout the Sacramento region and Northern California, and to expanding and increasing the number of novel therapies that can be brought to all patients who need them.”

What are your biggest hopes for the future at Cedars-Sinai?

Clive Svendsen, PhD: “That young investigators will get CIRM or NIH funding and be leaders in the regenerative medicine field.”

What do you hope is the future for stem cell research?

Pawash Priyank and Upasana Thakur: “We always have felt good about stem cell therapy. For us, a stem cell has transformed our lives completely. The correction of sequencing in the DNA taken out of Ronnie and injecting back in him has given him life. It has given him the immune system to fight infections. Seeing him grow without fear of doing anything, or going anywhere gives us so much happiness every hour. That’s the impact of stem cell research. With right minds continuing to research further in stem cell therapy bounded by certain good processes & laws around (so that misuse of the therapy couldn’t be done) will certainly change the way treatments are done for certain incurable diseases. I certainly see a bright future for stem cell research.”

On a personal note what is the moment that touched you the most in this journey.

Jan Nolta, PhD: “Each day a new patient or their story touches my heart. They are our inspiration for working hard to bring new options to their care through cell and gene therapy.”

Clive Svendsen, PhD: “When I realized we would get the funding to try and treat ALS with stem cells”

How important is it to raise awareness about stem cell research and to educate the next generation about it?

Pawash Priyank and Upasana Thakur: “Implementing stem cell therapy as a curriculum in the educational systems right from the beginning of middle school and higher could prevent false propaganda of it through social media. Awareness among people with accurate articles right from the beginning of their education is really important. This will also encourage the new generation to choose this as a subject in their higher studies and contribute towards more research to bring more solutions for a variety of diseases popping up every day.”

National Academy of Medicine honors CIRM Grantees

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As someone who is not always as diligent as he would like to be about sending birthday cards on time, I’m used to sending belated greetings to people. So, I have no shame in sending belated greetings to four CIRM grantees who were inducted into the National Academy of Medicine in 2020.

I say four, but it’s really three and a half. I’ll explain that later.

Being elected to the National Academy of Medicine is, in the NAM’s own modest opinion, “considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.”

To be fair, NAM is right. The people elected are among the best and brightest in their field and membership is by election from the other members of NAM, so they are not going to allow any old schmuck into the Academy (which could explain why I am still waiting for my membership).

The CIRM grantees elected last year are:

Dr. Antoni Ribas: Photo courtesy UCLA

Antoni Ribas, MD, PhD, professor of medicine, surgery, and molecular and medical pharmacology, U. C. Los Angeles.

Dr. Ribas is a pioneer in cancer immunology and has devoted his career to developing new treatments for malignant melanoma. When Dr. Ribas first started malignant melanoma was an almost always fatal skin cancer. Today it is one that can be cured.

In a news release Dr. Ribas said it was a privilege to be honored by the Academy: “It speaks to the impact immunotherapy has played in cancer research. When I started treating cases of melanoma that had metastasized to other organs, maybe 1 in 20 responded to treatment. Nobody in their right mind wanted to be a specialist in this field. It was the worst of the worst cancers.”

Looks like he chose his career path wisely.

Dr. Jeffrey Goldberg: Photo courtesy Stanford

Jeffrey Louis Goldberg, MD, PhD, professor and chair of ophthalmology, Stanford University, Palo Alto, Calif.

Dr. Goldberg was honored for his contribution to the understanding of vision loss and ways to reverse it. His lab has developed artificial retinas that transmit images down the optic nerve to the brain through tiny silicon chips implanted in the eye. He has also helped use imaging technology to better improve our ability to detect damage in photoreceptor cells (these are cells in the retina that are responsible for converting light into signals that are sent to the brain and that give us our color vision and night vision)

In a news release he expressed his gratitude saying: “I look forward to serving the goals of the National Academies, and to continuing my collaborative research efforts with my colleagues at the Byers Eye Institute at Stanford and around the world as we further our efforts to combat needless blindness.”

Dr. Mark Anderson; photo courtesy UCSF

Mark S. Anderson, MD, PhD, professor in Diabetes Research, Diabetes Center, U. C. San Francisco.

Dr. Anderson was honored for being a leader in the study of autoimmune diseases such as type 1 diabetes. This focus extends into the lab, where his research examines the genetic control of autoimmune diseases to better understand the mechanisms by which immune tolerance is broken.

Understanding what is happening with the immune system, figuring out why it essentially turns on the body, could one day lead to treatments that can stop that, or even reverse it by boosting immune activity.

Dr. John Dick: Photo courtesy University Health Network, Toronto

Remember at the beginning I said that three and a half CIRM grantees were elected to the Academy, well, Canadian researcher, Dr. John Dick is the half. Why? Well, because the award we funded actually went to UC San Diego’s Dennis Carson but it was part of a Collaborative Funding Partnership Program with Dr. Dick at the University of Toronto. So, we are going to claim him as one of our own.

And he’s a pretty impressive individual to partner with. Dr. Dick is best known for developing a test that led to the discovery of leukemia stem cells. These are cells that can evade surgery, chemotherapy and radiation and which can lead to patients relapsing after treatment. His work helped shape our understanding of cancer and revealed a new strategy for curing it.

Building a better brain (model) in the lab

Leica Picture of a brain organoid: courtesy National Institute of Allergy and Infectious Diseases, NIH

One of the biggest problems with trying to understand what is happening in a disease that affects the brain is that it’s really difficult to see what is going on inside someone’s head. People tend to object to you trying to open their noggin while they are still using it.

New technologies can help, devices such as MRI’s – which chart activity and function by measuring blood flow – or brain scans using electroencephalograms (EEGs), which measure activity by tracking electrical signaling and brain waves. But these are still limited in what they can tell us.

Enter brain organoids. These are three dimensional models made from clusters of human stem cells grown in the lab. They aren’t “brains in a dish” – they can’t function or think independently – but they can help us develop a deeper understanding of how the brain works and even why it doesn’t always work as well as we’d like.

Now researchers at UCLA’s Broad Center of Regenerative Medicine have created brain organoids that demonstrate brain wave activity similar to that found in humans, and even brain waves found in particular neurological disease.

The team – with CIRM funding – took skin tissue from healthy individuals and, using the iPSC method – which enables you to turn these cells into any other kind of cell in the body – they created brain organoids. They then studied both the physical structure of the organoids by examining them under a microscope, and how they were functioning by using a probe to measure brain wave activity.

In a news release Dr. Ranmal Samarasinghe, the first author of the study in the journal Nature Neuroscience, says they wanted to do this double test for a very good reason: “With many neurological diseases, you can have terrible symptoms but the brain physically looks fine. So, to be able to seek answers to questions about these diseases, it’s very important that with organoids we can model not just the structure of the brain but the function as well.”

Next, they took skin cells from people with a condition called Rhett syndrome. This is a rare genetic disorder that affects mostly girls and strikes in the first 18 months of life, having a severe impact on the individual’s ability to speak, walk, eat or even breathe easily. When the researchers created brain organoids with these cells the structure of the organoids looked similar to the non-Rhett syndrome ones, but the brain wave activity was very different. The Rhett syndrome organoids showed very erratic, disorganized brain waves.

When the team tested an experimental medication called Pifithrin-alpha on the Rhett organoids, the brain waves became less erratic and more like the brain waves from the normal organoids.

“This is one of the first tangible examples of drug testing in action in a brain organoid,” said Samarasinghe. “We hope it serves as a stepping stone toward a better understanding of human brain biology and brain disease.”

Celebrating a young life that almost wasn’t

Often on the Stem Cellar we feature CIRM-funded work that is helping advance the field, unlocking some of the secrets of stem cells and how best to use them to develop promising therapies. But every once in a while it’s good to remind ourselves that this work, while it may often seem slow, is already saving lives.

Meet Ja’Ceon Golden. He was one of the first patients treated at U.C. San Francisco, in partnership with St. Jude Children’s Hospital in Memphis, as part of a CIRM-funded study to treat a rare but fatal disorder called Severe Combined Immunodeficiency (SCID). Ja’Ceon was born without a functioning immune system, so even a simple cold could have been fatal.

At UCSF a team led by Dr. Mort Cowan, took blood stem cells from Ja’Ceon and sent them to St. Jude where another team corrected the genetic mutation that causes SCID. The cells were then returned to UCSF and re-infused into Ja’Ceon.  

Over the next few months those blood stem cells grew in number and eventually helped heal his immune system.

He recently came back to UCSF for more tests, just to make sure everything is OK. With him, as she has been since his birth, was his aunt and guardian Dannie Hawkins. She says Ja’Ceon is doing just fine, that he has just started pre-K, is about to turn five years old and in January will be five years post-therapy. Effectively, Ja’Ceon is cured.

SCID is a rare disease, there are only around 70 cases in the US every year, but CIRM funding has helped produce cures for around 60 kids so far. A recent study in the New England Journal of Medicine showed that a UCLA approach cured 95 percent of the children treated.

The numbers are impressive. But not nearly as impressive, or as persuasive of the power of regenerative medicine, as Ja’Ceon and Dannie’s smiles.

Ja’Ceon on his first day at pre-K. He loved it.

Latest CIRM TRAN1 awards focus on CAR-based cell therapy to treat cancer

Earlier this week the CIRM ICOC Board awarded $14.5 million to fund three translational stage research projects (TRAN1), whose goal is to support early development activities necessary for advancement to a clinical study or broad end use of a potential therapy. Although all three projects have their distinct area of focus, they all utilize CAR-based cell therapy to treat a certain type of cancer. This approach involves obtaining T cells, which are an immune system cell that can destroy foreign or abnormal cells, and modifying them with a chimeric antigen receptor (CAR). This enables the newly created CAR-engineered cells to identify specific tumor signals and destroy the cancer. In the sections below we will take a deeper look at each one of these recently approved projects.

TRAN1-12245

Image Description: Hideho Okada, M.D., Ph.D.

$2,663,144 was awarded to the University of California, San Francisco (UCSF) to develop specialized CAR-T cells that are able to recognize and destroy tumor cells in glioblastoma, an aggressive type of cancer that occurs in the brain and spinal cord. The specialized CAR-T cells have been created such that they are able to detect two specific signals expressed in glioblastoma. Hideho Okada, M.D., Ph.D. and his team at UCSF will test the therapy in mice with human glioblastoma grafts. They will be looking at preclinical safety and if the CAR-T cell therapy is able to produce a desired or intended result.

TRAN1-12250

Image Description: Lili Yang, Ph.D.

$5,949,651 was awarded to the University of California, Los Angeles (UCLA) to develop specialized CAR-engineered cells from human blood stem cells to treat multiple myeloma, a type of blood cancer. Lili Yang, Ph.D. and her team have developed a method using human blood stem cells to create invariant natural killer T (iNKT) cells, a special kind of T cell with unique features that can more effectively attack tumor cells using multiple mechanisms and migrate to and infiltrate tumor sites. After being modified with CAR, the newly created CAR-iNKT cells are able to target a specific signal present in multiple myeloma. The team will test the therapy in mice with human multiple myeloma. They will be looking at preclinical safety and if the CAR-iNKT cells are able to produce a desired or intended result.

TRAN1-12258

Image Description: Cristina Puig-Saus, Ph.D.

Another $5,904,462 was awarded to UCLA to develop specialized CAR-T cells to treat melanoma, a form of skin cancer. Cristina Puig-Saus, Ph.D. and her team will use naïve/memory progenitor T cells (TNM), a subset of T cells enriched with stem cells and memory T cells, an immune cell that remains long after an infection has been eliminated. After modification with CAR, the newly created CAR-TNM cells will target a specific signal present in melanoma. The team will test the therapy in mice with human melanoma. They will be looking at preclinical safety and if the CAR-TNM cells are able to produce a desired or intended result.

CIRM Board Approves Continued Funding for SPARK and Alpha Stem Cell Clinics

Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved $8.5 million to continue funding of the Summer Program to Accelerate Regenerative Medicine Knowledge (SPARK) and Alpha Stem Cell Clinics (ASCC).

This past February, the Board approved continued funding for stem cell focused educational programs geared towards undergraduate, masters, pre/postdoctoral, and medical students. The SPARK program is an existing CIRM educational program that provides for a summer internship for high school students.

To continue support for SPARK, the Board has approved $5.1 million to be allocated to ten new awards ($509,000 each) with up to a five-year duration to support 500 trainees.  The funds will enable high school students all across California to directly take part in summer research at various institutions with a stem cell, gene therapy, or regenerative medicine focus.  The goal of these programs is to prepare and inspire the next generation of scientists and provide opportunities for California’s diverse population, including those who might not have the opportunity to take part in summer research internships due to socioeconomic constraints.

CIRM’s ASCC Network is a unique regenerative medicine-focused clinical trial network that currently consists of five medical centers across California who specialize in accelerating stem cell and gene-therapy clinical trials by leveraging of resources to promote efficiency, sharing expertise, and enhancing chances of success for the patients. To date, over 105 trials in various disease indications have been supported by the ASCC Network.  While there are plans being developed for a significant ASCC Network expansion by some time next year, funding for all five sites has ended or are approaching the end of their current award period. To maintain the level of activity of the ASCC Network until expansion funding is available next year, the Board approved $3.4 million to be allocated to five supplemental awards (up to $680,000 each) in order to provide continued funding to all five sites; the host institutions will be required to match the CIRM award.  These funds will support talent retention and program key activities such as the coordination of clinical research, management of patient and public inquiries, and other operational activities vital to the ASCC Network.

“Education and infrastructure are two funding pillars critical for creating the next generation of researchers and conducting stem cell based clinical trials” says Maria T. Millan, M.D., President and CEO of CIRM.  “The importance of these programs was acknowledged in Proposition 14 and we expect that they will continue to be important components of CIRM’s programs and strategic direction in the years to come.”

The Board also awarded $14.5 million to fund three translational stage research projects (TRAN1), whose goal is to support early development activities necessary for advancement to a clinical study or broad end use of a potential therapy.

The awards are summarized in the table below:

ApplicationTitleInstitution Award
TRAN1-12245  Development of novel synNotch CART cell therapy in patients with recurrent EGFRvIII+ glioblastoma    UCSF    $2,663,144
TRAN1-12258  CAR-Tnm cell therapy for melanoma targeting TYRP-1    UCLA  $5,904,462  
TRAN1-12250HSC-Engineered Off-The-Shelf CAR-iNKT Cell Therapy for Multiple Myeloma  UCLA  $5,949,651

New Study Shows CIRM-Supported Therapy Cures More than 95% of Children Born with a Fatal Immune Disorder

Dr. Donald B. Kohn; Photo courtesy UCLA

A study published in the New England Journal of Medicine shows that an experimental form of stem cell and gene therapy has cured 48 of 50 children born with a deadly condition called ADA-SCID.

Children with ADA-SCID, (severe combined immunodeficiency due to adenosine deaminase deficiency) lack a key enzyme that is essential for a healthy, functioning immune system. As a result, even a simple infection could prove fatal to these children and, left untreated, most will die within the first two years of life.

In the study, part of which was supported by CIRM, researchers at the University of California Los Angeles (UCLA) and Great Ormond Street Hospital (GOSH) in London took some of the children’s own blood-forming stem cells and, in the lab, corrected the genetic mutation that causes ADA-SCID. They then returned those cells to the children. The hope was that over time the corrected stem cells would create a new blood supply and repair the immune system.

In the NEJM study the researchers reported outcomes for the children two and three years post treatment.

“Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging,” said Dr. Don Kohn, a distinguished professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems.”

Two of the children did not respond to the therapy and both were returned to the current standard-of-care therapy. One subsequently underwent a bone marrow transplant. None of the children in the study experienced serious side-effects.

“This is encouraging news for all families affected by this rare but deadly condition,” says Maria T. Millan, MD, President and CEO of CIRM. “It’s also a testament to the power of persistence. Don Kohn has been working on developing this kind of therapy for 35 years. To see it paying off like this is a remarkable testament to his skill as a researcher and determination to help these patients.”

Hitting our Goals: Accelerating to the finish line

Way, way back in 2015 – seems like a lifetime ago doesn’t it – the team at CIRM sat down and planned out our Big 6 goals for the next five years. The end result was a Strategic Plan that was bold, ambitious and set us on course to do great things or kill ourselves trying. Well, looking back we can take some pride in saying we did a really fine job, hitting almost every goal and exceeding them in some cases. So, as we plan our next five-year Strategic Plan we thought it worthwhile to look back at where we started and what we achieved. Goal #6 was Accelerate.

Ever wonder how long it takes for a drug or therapy to go from basic research to approval by the US Food and Drug Administration (FDA)? Around 12 years on average is the answer. That’s a long time. And it can take even longer for stem cell therapies to go that same distance.

There are a lot of reasons why it takes so long (safety being a hugely important element) but when we were sitting down in 2015 to put together our Strategic Plan we wanted to find a way to speed up that process, to go faster, without in any way reducing the focus on safety.

So, we set a goal of reducing the time it takes from identifying a stem cell therapy candidate to getting an Investigational New Drug (IND) approval from the FDA, which means it can be tested in a clinical trial. At the time it was taking us around eight years, so we decided to go big and try to reduce that time in half, to four years.

Then the question was how were we going to do that? Well, before we set the goal we did a tour of the major biomedical research institutions in California – you know, University of California Los Angeles (UCLA) UC San Francisco, Stanford etc. – and asked the researchers what would help them most. Almost without exception said “a clearing house”, a way to pair early stage investigators with later stage partners who possess the appropriate expertise and interest to advance the project to the next stage of development, e.g., helping a successful basic science investigator find a qualified partner for the project’s translational research phase.

So we set out to do that. But we didn’t stop there. We also created what we called Clinical Advisory Panels or CAPs. These consisted of a CIRM Science Officer with expertise on a particular area of research, an expert on the kind of research being done, and a Patient Representative. The idea was that CAPs would help guide and advise the research team, helping them overcome specific obstacles and get ready for a clinical trial. The Patient Representative could help the researchers understand what the needs of the patient community was, so that a trial could take those into account and be more likely to succeed. For us it wasn’t enough just to fund promising research, we were determined to do all we could to support the team behind the project to advance their work.

How did we do. Pretty good I would have to say. For our Translational stage projects, the average amount of time it took for them to move to the CLIN1 stage, the last stage before a clinical trial, was 4.18 years. For our CLIN1 programs, 73 percent of those achieved their IND within 2 years, meaning they were then ready to actually start an FDA-sanctioned clinical trial.

Of course moving fast doesn’t guarantee that the therapy will ultimately prove effective. But for an agency whose mission is “to accelerate stem cell therapies to patients with unmet medical needs”, going slow is not an option.

CIRM funded stem cell therapy could one day help stroke and dementia patients

Image Description: Microscope images showing brain tissue that has been damaged by white matter stroke (left) and then repaired by the new glial cell therapy (right). Myelin (seen in red), is a substance that protects the connections between neurons and is lost due to white matter stroke. As seen at right, the glial cell therapy (green) restores lost myelin and improves connections in the brain. | Credit: UCLA Broad Stem Cell Research Center/Science Translational Medicine

Dementia is a general term that describes problems with memory, attention, communication, and physical coordination. One of the major causes of dementia is white matter strokes, which occurs when multiple strokes (i.e. a lack of blood supply to the brain) gradually damages the connecting areas of the brain (i.e. white matter).

Currently, there are no therapies capable of stopping the progression of white matter strokes or enhancing the brain’s limited ability to repair itself after they occur.

However, a CIRM-funded study ($2.09 million) conducted by S. Thomas Carmichael, M.D., Ph.D. and his team at UCLA showed that a one-time injection of an experimental stem cell therapy can repair brain damage and improve memory function in mice with conditions that mimic human strokes and dementia.

The therapy consists of glial cells, which are a special type of cell present in the central nervous system that surround and protect neurons. The glial cells are derived from induced pluripotent stem cells (iPSCS), stem cells that are derived from skin or blood cells through the process of reprogramming and have the ability to become virtually any type of cell.

Dr. Carmichael and his team injected the newly developed glial cells into the brains of mice that had damage similar to humans in the early to middle stages of dementia. The team found that the cell therapy traveled to the damaged areas of the brain and secreted chemicals that stimulated the brain’s own stem cells to start repairing the damage. This not only limited the progression of damage, but also enhanced the formation of new neural connections and increased the production of myelin, a fatty substance that covers and protects neurons.

In a press release from UCLA, Francesca Bosetti, Ph.D., Pharm.D., Program Director at the National Institute of Neurological Disorders and Strokes, was optimistic about what these findings could mean for patients with strokes or dementia.

“These preliminary results suggest that glial cell-based therapies may one day help combat the white matter damage that many stroke and vascular dementia patients suffer every year.”

Another interesting finding from this study is that even if the injected cells were eliminated a few months after they had been transplanted, the mice’s recovery was unaffected. The researchers believe that this indicates that the therapy primarily serves as a way to stimulate the brain’s own repair process.

In the same press release, Dr. Carmichael elaborates on this concept.

“Because the cell therapy is not directly repairing the brain, you don’t need to rely on the transplanted cells to persist in order for the treatment to be successful.”

The team is now conducting the additional studies necessary to apply to the Food and Drug Administration (FDA) for permission to test the therapy in a clinical trial in humans. If the therapy is shown to be safe and effective through clinical trials in humans, the team envisions that it could be used at hospitals as a one-time treatment for people with early signs of white matter stroke.

The full results of this study were published in Science Translational Medicine.

CIRM funding helps improve immune cell therapy to combat HIV

Image description: T cell infected with HIV.
Image Credit: National Institute of Allergy and Infectious Diseases (NIAID)

In June of last year we wrote about how Dr. Scott Kitchen and his team at UCLA are engineering blood forming stem cells in order to fight HIV, a potentially deadly virus that attacks the immune system and can worsen into AIDS if left untreated. HIV causes havoc in the body by attacking T cells, a vital part of the body’s immune system that helps fight off infections and diseases.

Dr. Kitchen’s approach uses what is called Chimeric Antigen Receptor (CAR) T gene therapy. This is a type of immune therapy that involves genetically modifying the body’s own blood forming stem cells to create T cells that have the ability to fight HIV. These newly formed immune cells have the potential to not only destroy HIV-infected cells but to create “memory cells” that could provide lifelong protection from HIV infection.

Flash forward to April of this year and the results of the CIRM funded study ($1.7M) have been published in PLOS Pathogens.

Unfortunately, although the previously designed CAR T gene therapy was still able to create HIV fighting immune cells, the way the CAR T gene therapy was designed still had the potential to allow for HIV infection.

For this new study, the team modified the CAR T gene therapy such that the cells would be resistant to infection and allow for a more efficient and longer-lasting cell response against HIV than before.

While the previous approach allowed for the continuous production of new HIV-fighting T cells that persisted for more than two years, these cells are inactivated until they come across the HIV virus. The improved CAR T gene therapy engineers the body’s immune response to HIV rather than waiting for the virus to induce a response. This is similar in concept to how a vaccine prepares the immune system to respond against a virus. The new approach also creates a significant number of “memory” T cells that are capable of quickly responding to reactivated HIV. 

The hope is that these findings can influence the development of T cells that are able carry “immune system” memory with the ability to recognize and kill virus-infected or cancerous cells. 

To date, CIRM has also funded four separate clinical trials related to the treatment of HIV/AIDS totaling over $31 million.