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.  

Funding a Clinical Trial for a Functional Cure for HIV

The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.

This is the 82nd clinical trial funded by CIRM.

There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.

The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.

Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.

“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”

In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”

The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.

CIRM has already invested almost $81 million in 20 projects targeting HIV/AIDS, including four clinical trials.

How CIRM contributed to City of Hope study helping man with HIV into long-term remission

The news that a stem cell transplant at City of Hope helped a man with HIV go into long-term remission made banner headlines around the world. As it should. It’s a huge achievement, particularly as the 66-year-old man had been living with HIV since 1988.

What wasn’t reported was that work supported by the California Institute for Regenerative Medicine played a role in making that happen.

The Stem Cell Transplant

First the news. In addition to living with HIV the man was diagnosed with acute leukemia. Doctors at City of Hope found a donor who was not only a perfect match to help battle the patient’s leukemia, but the donor also had a rare genetic mutation that meant they were resistant to most strains of HIV.

In transplanting blood stem cells from the donor to the patient they were able to send both his leukemia and HIV into remission. The patient stopped taking all his antiretroviral medications 17 months ago and today has no detectable levels of HIV.

In a news release  City of Hope hematologist Ahmed Aribi, M.D., said the patient didn’t experience any serious complications after the procedure.

“This patient had a high risk for relapsing from AML [acute myeloid leukemia], making his remission even more remarkable and highlighting how City of Hope provides excellent care treating complicated cases of AML and other blood cancers.”

It’s a remarkable achievement and is only the fifth time that a patient with both HIV and leukemia has been put into remission after a transplant from an HIV-resistant donor.

CIRM’s Contribution

So, what does that have to do with CIRM? Well, CIRM’s Alpha Clinics Network helped City of Hope get this case approved by an Institutional Review Board (IRB) and also helped in collecting and shipping the donor blood. In addition, part of the Alpha Clinics team at University of California San Diego helped with the reservoir analysis of blood and gut biopsies to check for any remaining signs of HIV.

It’s a reminder that this kind of achievement is a team effort and CIRM is very good at creating and supporting teams. The Alpha Clinics Network is a perfect example. We created it because there was a need for a network of world-class medical facilities with the experience and expertise to deliver a whole new kind of therapy. The Network has been remarkably successful in doing that with more than 200 clinical trials, taking care of more than 1,000 patients, and treating more than 40 different diseases.

This year our Board approved expanding the number of these clinics to better serve the people of California.

While the role of the Alpha Clinics Network in helping this one patient may seem relatively small, it was also an important one. And we are certainly not stopping here. We have invested more than $79 million in 19 different projects targeting HIV/AIDS, include four clinical trials.

We are in this for the long term and results like the man who had HIV and is now in remission are a sign we are heading in the right direction.

UC Davis Health researchers aim to use CAR T cells for HIV cure

Dr. Abedi (right) in the lab at UC Davis Health. He and his team of researchers have launched a study looking to identify a potential cure for HIV. Photo Courtesy of UC Davis Health.

Worldwide, almost 38 million people are living with HIV—the virus that can lead to AIDS— and it’s estimated that 75% of them receive antiviral treatment to keep the virus in check. In California, 150,000 people live with HIV and 68% of these individuals are virally suppressed due to treatment.  

To fight this virus, UC Davis Health researchers—with funding from a CIRM grant—have launched a study looking to identify a potential cure for HIV. Using immunotherapy, researchers will take a patient’s own white blood cells, called T-cells, and modify them so that they can identify and target HIV cells to control the virus without medication. 

Targeting HIV with CAR T cells

“For this study we will educate the cells by inserting a gene to target cells that have been infected by the HIV virus,” explained Mehrdad Abedi, professor of internal medicine, hematology and oncology and the principal investigator of the study. “The idea is these modified cells will attach to the HIV-infected cells and destroy the cells that are infected while also stopping the infected cells’ ability to replicate.” 

Modified T-cells, known as CAR T cells, are an FDA-approved treatment for different forms of cancer including acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma. With cancer, the immune system often fails to deploy T-cells right away or at all. When it does, the attack is ineffective. CAR T-cell immunotherapy changes these collected T-cells to produce chimeric antigen receptors (or CARs) that adhere to tumors to destroy them. 

Study seeking HIV patients

For the study, UC Davis Health researchers are working to identify and recruit HIV-positive patients between the ages of 18 and 65 who have had an undetectable HIV viral load for the 12 months and have been on continuous antiretroviral therapy for at least 12 months.  

Patients also need to be willing to pause their antiretroviral therapy as part of the study. 

“While it is exciting, the study will require a lot of dedication from the patient because of the time commitment involved and the necessary steps required,” said Paolo Troia-Cancio, a clinical professor of medicine with the infectious disease division with over 20 years of experience treating HIV and co-investigator on the CAR T cell study.   

The search for an HIV cure 

Three patients have been cured of HIV using bone marrow transplants, including a woman in New York who received a cord blood stem cell transplant. She received a bone marrow transplant using umbilical cord blood donor cells that bore a mutation that makes them resistant to HIV infection to treat her leukemia. 

There have also been two previous cases involving an HIV cure following allogeneic bone marrow transplants. Both patients had leukemia and received bone marrow transplants from donors who carried the same mutation that blocks HIV infection.  

“While these stories provide inspiration and hope to finding a cure for HIV, a bone marrow transplant is not a realistic option for most patients,” said Abedi. “Such transplants are highly invasive and risky, so they are generally offered only to people with cancer who have exhausted all other options.” 

Abedi and his fellow researchers see this study as a potential road map to finding a cure for HIV.  

The California Institute for Regenerative Medicine (CIRM) has funded earlier work by Dr. Abedi and his team in trying to develop a therapy to help people with HIV who also have lymphoma.  

To read the source article about this CIRM-funded study, click here

The Evolution of World AIDS Day: Then and Now 

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TIME cover stories on AIDS through the years

A truly modern epidemic, HIV/AIDS has hit every continent on the planet and affects nearly 40 million people worldwide. Today, we celebrate World AIDS Day by commemorating those who have died from AIDS-related illness, showing support for people living with HIV, and fighting for a cure. 

World AIDS Day was first observed in 1988 and takes place on December 1st each year. The first ever global health day, the path to acceptance and scientific advancements towards HIV/AIDS hasn’t been easy. Over the past four decades, the epidemic has changed enormously and so, too, has the global agenda. Universal testing is the main key to halting the number of new infections. Scientific advances in HIV treatment have prolonged lives and, in many cases, even made the virus undetectable. But this battle is far from over. 

40 years ago, in the spring of 1981, a mystery illness began exploding across the gay communities of New York, Los Angeles and San Francisco. Men were inexplicably coming down with cancer and other mysterious illnesses. Many of them would be dead within weeks. As more cases were confirmed across the Atlantic, it become known as the ‘gay plague’. It wasn’t until 1982 that this mysterious plague earned a name: Acquired Immune Deficiency Syndrome or AIDS. The following year, scientists uncovered the culprit behind AIDS. It was a virus, which they eventually called HIV: the human immunodeficiency virus

And the disease wasn’t just targeting homosexuals. Anyone could be infected through blood, sexual intercourse, pregnancy, and breastfeeding. However, word was to slow get out and ignorance about HIV remained rampant. By 1984, as the death toll climbs, the top priority become preventing the spread of AIDS.

As the science progressed, activism intensified. AIDS patients and their loved ones began uniting all over the world to demand greater access to experimental drugs and plead their governments for more funding. In 1990, Congress passed the largest federally funded program in the US for people living with HIV/AIDS through the Ryan White CARE Act. In 1993, President Clinton set up the White House Office of National AIDS Policy and the National Institute of Health (NIH) expanded its AIDS research.

With great funding came great scientific breakthroughs for the treatment and prevention of HIV. FDA’s approval of Atripla in 2006 marked a watershed in HIV treatment. By combining three different antiviral medications- efavirenz, emtricitabine and tenofovir- into a single fixed-dose combination pill, HIV treatment became a once-daily single tablet regimen. Between 2005 and 2018, there was a 45% decline in AIDS related deaths worldwide.

Despite tremendous biomedical and scientific progress, there’s still no cure for AIDS. As people with HIV live longer, AIDS is a topic that has drifted from the headlines. When World AIDS Day was first established in 1988, the world looked very different to how it is today. As we celebrate the progress of the past four decades on this historic day, we mustn’t lose sight of the ultimate goal that lays ahead of us. CIRM has committed nearly $80 million to HIV/AIDS research including funding four separate clinical trials.

Inspiring new documentary about stem cell research

Poster for the documentary “Ending Disease”

2020 has been, to say the very least, a difficult and challenging year for all of us. But while the focus of the world has, understandably, been on the coronavirus there was also some really promising advances in stem cell research. Those advances are captured in a great new documentary called Ending Disease.

The documentary is by Emmy award-winning filmmaker Joe Gantz. In it he follows ten people who are facing life-threatening or life-changing diseases and injuries and who turn to pioneering stem cell therapies for help.

It’s an inspiring documentary, one that reminds you of the real need for new treatments and the tremendous hope and promise of stem cell therapies. Here’s a look at a trailer for Ending Disease.

You can see an exclusive screening of Ending Disease on Friday, January 8th, 2021 at 5:00pm PST.

After the livestream, there will be a live Q&A session where former members of the successful Proposition 14 campaign team – which refunded CIRM with an additional $5.5 billion – will be joined by CIRM’s President and CEO Dr. Maria Millan, talking about what lies ahead for CIRM and the future of stem cell research.

To purchase a ticket, click here. It only costs $12 and 50% of the ticket sales proceeds will go to Americans for Cures to help them continue to advocate for the advancement of stem cell research, and more importantly, for the patients and families to whom stem cell research provides so much hope.

If you need any extra persuading that it’s something you should definitely put on our calendar, here’s a letter from the film maker Joe Gantz.

I am the director of the documentary Ending Disease: The Stem Cell, Anti-Cancer T-Cell, & Antibody Revolution In Medicine, a film that will help inform people about the progress that’s been made in this field and how people with their lives on the line are now able to benefit from these new regenerative therapies. 

I was granted unprecedented access to ten of the first generation of clinical trials using stem cell and regenerative medicine to treat and cure many of the most devastating diseases and conditions including: brain cancer, breast cancer, leukemia and lymphoma, HIV, repairing a broken spinal cord, retinitis pigmentosa and SCID. The results are truly inspiring.

This is personal for me.  After spending four years making this documentary, I was diagnosed with bladder cancer. Upon diagnosis, I immediately felt the same desperation as millions of families who are in search of a medical breakthrough. I understood, on a personal level, what the patients we followed in the film all knew: when you are diagnosed with a disease, there is a narrow window of time in which you can effectively seek a life-saving treatment or cure. If treatment becomes available outside of that window, then it is too late. However, Ending Disease shows that with continued support for regenerative medicine, we can create a near future in which one-time cures and highly mitigating therapies are available to patients for a whole host of diseases.

Best regards,

Joe

Remembering a stem cell pioneer in the fight against HIV/AIDS

Timothy Ray Brown. Photo courtesy Seattle Times

Timothy Ray Brown, a man who was the first person to be cured of HIV, giving hope to millions of people around the world, died at his home in Palm Springs this week. He was just 54 years old.

For years Brown was known simply as “the Berlin patient” because that was where he was living when he made medical history. He was diagnosed with HIV in 1995 and began taking medications to keep the virus under control. He was later also diagnosed with leukemia. He underwent several rounds of treatment for the leukemia, but it kept recurring.

By 2007 Brown’s physician decided the best way to treat the leukemia was with a blood stem cell transplant. But the doctor also wanted to see if using the stem cells from a donor who had a natural immunity to the AIDS virus could help treat Brown’s HIV. While such donors are very rare, the doctor succeeded in finding one whose bone marrow carried the CCR5 gene, a mutation that is believed to provide resistance to HIV. The transplant was a success, putting Brown’s leukemia into remission and eliminating detectable traces of HIV. For the first time in years he was able to stop taking the medications that had helped keep the virus under control.

The procedure quickly garnered world-wide attention. But not everyone was convinced it was real. Some questioned if Brown’s HIV had really been eradicated and speculated that the virus was merely suppressed. But with each passing year, and no signs of the virus recurring, more and more people came to believe it was a cure.

Initially Brown remained in the background, preferring not to be identified. But three years after his transplant he decided he had to come forward and put a face on “the Berlin patient”. In an interview with the website ContagionLive he explained why:

“At some point, I decided I didn’t want to be the only person in the world cured of H.I.V.,” I wanted there to be more. And the way to do that was to show the world who I am and be an advocate for H.I.V.”

He proved to be a powerful advocate, talking at international conferences and serving as living-proof that stem cells could help lead to a cure for HIV.

But while he managed to beat HIV, he could not beat leukemia. He suffered relapses that required another transplant and a difficult recovery. When it returned again this time, there was little physicians could do.

But Timothy Ray Brown did get to see his hope of not being the only patient cured seemingly come true. In September of last year researchers announced they had successfully treated a second person, known as “the London patient” using the same technique that cured Brown.

While it wasn’t the role he would have chosen Brown was a pioneer. His experience showed that a deadly virus could be cured. His courage in not just overcoming the virus but in overcoming his own reluctance to take center stage and becoming a symbol of hope for millions remain and will never die.  

Since Brown’s transplant many other scientists have attempted to replicate the procedure that cured Brown, in the hopes of making it available to many more people.

CIRM has funded three clinical trials targeting HIV, two of which are still active. Dr. Mehrdad Abedi at UC Davis and Dr. John Zaia at City of Hope are both using the patient’s own blood forming stem cells to try and defeat the virus.

If they succeed, some of the credit should go to Timothy Ray Brown, the man who led the way.

Charting a new course for stem cell research

What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.

Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.

The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?

It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.

We’ll hear what’s being done to find therapies for

  • Rare diseases that affect children
  • Type 1 diabetes
  • HIV/AIDS
  • Glioblastoma
  • Multiple myeloma

We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.

It’s going to be a fascinating day. And did I mention it’s free!

All you have to do is go to this Eventbrite page to register.

And feel free to share this with your family, friends or anyone you think might be interested.

We look forward to seeing you there.

Scientists Engineer Stem Cells to Fight HIV

Image of the virus that causes AIDS – courtesy NIH

If that headline seems familiar it should. It came from an article in MIT Technology Review back in 2009. There have been many other headlines since then, all on the same subject, and yet here we are, in 2020, and still no cure for HIV/AIDS. So what’s the problem, what’s holding us back?

First, the virus is incredibly tough and wily. It is constantly mutating so trying to target it is like playing a game of ‘whack a mole’. Secondly not only can the virus evade our immune system, it actually hijacks it and uses it to help spread itself throughout the body. Even new generations of anti-HIV medications, which are effective at controlling the virus, can’t eradicate it. But now researchers are using new tools to try and overcome those obstacles and tame the virus once and for all.

Dr. Scott Kitchen: Photo David Geffen School of Medicine, UCLA

UCLA researchers Scott Kitchen and Irvin Chen have been awarded $13.65 million by the National Institutes of Health (NIH) to see if they can use the patient’s own immune system to fight back against HIV.

Dr. Irvin Chen: Photo UCLA

Dr. Kitchen and Dr. Chen take the patient’s own blood-forming stem cells and then, in the lab, they genetically engineer them to carry proteins called chimeric antigen receptors or CARs. Once these blood cells are transplanted back into the body, they combine with the patient’s own immune system T cells (CAR T). These T cells now have a newly enhanced ability to target and destroy HIV.

That’s the theory anyway. Lots of research in the lab shows it can work. For example, the UCLA team recently showed that these engineered CAR T cells not only destroyed HIV-infected cells but also lived for more than two years. Now the team at UCLA want to take the lessons learned in the lab and apply them to people.

In a news release Dr. Kitchen says the NIH grant will give them a terrific opportunity to do that: “The overarching goal of our proposed studies is to identify a new gene therapy strategy to safely and effectively modify a patient’s own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection. It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.”

By the way, CIRM helped get this work off the ground with an early-stage grant. That enabled Dr. Kitchen and his team to get the data they needed to be able to apply to the NIH for this funding. It’s a great example of how we can kick-start projects that no one else is funding. You can read a blog about that early stage research here.

CIRM has already funded three clinical trials targeting HIV/AIDS. Two of these are still active; Dr. Mehrdad Abedi at UC Davis and Dr. John Zaia at City of Hope.

71 for Proposition 71

Proposition 71 is the state ballot initiative that created California’s Stem Cell Agency. This month, the Agency reached another milestone when the 71st clinical trial was initiated in the CIRM Alpha Stem Cell Clinics (ASCC) Network. The ASCC Network deploys specialized teams of doctors, nurses and laboratory technicians to conduct stem cell clinical trials at leading California Medical Centers.

StateClinics_Image_CMYK

These teams work with academic and industry partners to support patient-centered for over 40 distinct diseases including:

  • Amyotrophic Lateral Sclerosis (ALS)
  • Brain Injury & Stroke
  • Cancer at Multiple Sites
  • Diabetes Type 1
  • Eye Disease / Blindness Heart Failure
  • HIV / AIDS
  • Kidney Failure
  • Severe Combined Immunodeficiency (SCID)
  • Sickle Cell Anemia
  • Spinal Cord Injury

These clinical trials have treated over 400 patients and counting. The Alpha Stem Cell Clinics are part of CIRM’s Strategic Infrastructure. The Strategic Infrastructure program which was developed to support the growth of stem cell / regenerative medicine in California. A comprehensive update of CIRM’s Infrastructure Program was provided to our Board, the ICOC.

CIRM’s infrastructure catalyzes stem cell / regenerative medicine by providing resources to all qualified researchers and organizations requiring specialized expertise. For example, the Alpha Clinics Network is supporting clinical trials from around the world.

Many of these trials are sponsored by commercial companies that have no CIRM funding. To date, the ASCC Network has over $27 million in contracts with outside sponsors. These contracts serve to leverage CIRMs investment and provide the Network’s medical centers with a diverse portfolio of clinical trials to address patients’’ unmet medical needs.

Alpha Clinics – Key Performance Metrics

  • 70+ Clinical Trials
  • 400+ Patients Treated
  • 40+ Disease Indications
  • Over $27 million in contracts with commercial sponsors

The CIRM Alpha Stem Cell Clinics and broader Infrastructure Programs are supporting stem cell research and regenerative medicine at every level, from laboratory research to product manufacturing to delivery to patients. This infrastructure has emerged to make California the world leader in regenerative medicine. It all started because California’s residents supported a ballot measure and today we have 71 clinical trials for 71.