Throwback Thursday: Progress towards a cure for HIV/AIDS

Welcome to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded research and clinical trials that are aimed at developing stem cell-based treatments for HIV/AIDS.

 Tomorrow, December 1st, is World AIDS Day. In honor of the 34 million people worldwide who are currently living with HIV, we’re dedicating our latest #ThrowbackThursday blog to the stem cell research and clinical trials our Agency is funding for HIV/AIDS.

world_logo3To jog your memory, HIV is a virus that hijacks your immune cells. If left untreated, HIV can lead to AIDS – a condition where your immune system is compromised and cannot defend your body against infection and diseases like cancer. If you want to read more background about HIV/AIDs, check out our disease fact sheet.

Stem Cell Advancements in HIV/AIDS
While patients can now manage HIV/AIDS by taking antiretroviral therapies (called HAART), these treatments only slow the progression of the disease. There is no effective cure for HIV/AIDS, making it a significant unmet medical need in the patient community.

CIRM is funding early stage research and clinical stage research projects that are developing cell based therapies to treat and hopefully one day cure people of HIV. So far, our Agency has awarded 17 grants totalling $72.9 million in funding to HIV/AIDS research. Below is a brief description of four of these exciting projects:

Discovery Stage Research
Dr. David Baltimore at the California Institute of Technology is developing an innovative stem cell-based immunotherapy that would prevent HIV infection in specific patient populations. He recently received a CIRM Quest award, (a funding initiative in our Discovery Stage Research Program) to pursue this research.

CIRM science officer, Dr. Ross Okamura, oversees Baltimore’s CIRM grant. He explained how the Baltimore team is genetically modifying the blood stem cells of patients so that they develop into immune cells (called T cells) that specifically recognize and target the HIV virus.

Ross_IDCard

Ross Okamura, PhD

“The approach Dr. Baltimore is taking in his CIRM Discovery Quest award is to engineer human immune stem cells to suppress HIV infection.  He is providing his engineered cells with T cell protein receptors that specifically target HIV and then exploring if he can reduce the viral load of HIV (the amount of virus in a specific volume) in an animal model of the human immune system. If successful, the approach could provide life-long protection from HIV infection.”

While Baltimore’s team is currently testing this strategy in mice, if all goes well, their goal is to translate this strategy into a preventative HIV therapy for people.

Clinical Trials
CIRM is currently funding three clinical trials focused on HIV/AIDS led by teams at Calimmune, City of Hope/Sangamo Biosciences and UC Davis. Rather than spelling out the details of each trial, I’ll refer you to our new Clinical Trial Dashboard (a screenshot of the dashboard is below) and to our new Blood & Immune Disorders clinical trial infographic we released in October.

dashboardblooddisorders

MonthofCIRM_BloodDisordersJustHIV.png

As you can see from these projects, CIRM is committed to funding cutting edge research in HIV/AIDS. We hope that in the next few years, some of these projects will bear fruit and help advance stem cell-based therapies to patients suffering from this disease.

I’ll leave you with a few links to other #WorldAIDSDay relevant blogs from our Stem Cellar archive and our videos that are worth checking out.

 

CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.

CIRM Board member Jeff Sheehy appointed to the San Francisco Board of Supervisors

As a former journalist I love breaking news, it gets the adrenaline flowing. Usually when news is breaking it’s bad news. Today, however, I was fortunate to be present for breaking news that was, more than anything, a celebration.

sheehy_sfsupervisor1

Jeff Sheehy, CIRM Board member (standing at podium) was appointed today as San Francisco’s District 8 Supervisor by Mayor Ed Lee (right of Sheehy), replacing Scott Weiner (3rd from left) who held the position before his election to the State Senate

San Francisco Mayor Ed Lee today appointed CIRM Board member, and Patient Advocate for HIV/AIDS, Jeff Sheehy, as the new Supervisor for District 8. In announcing his decision the Mayor said:

edlee.jpg

SF Mayor Ed Lee

“This was a very important decision. I was looking for someone who is passionate, a lover of our City and our people, someone who is solution oriented. I found that person in Jeff Sheehy. He has passion and commitment. He has an intellect that is very deep and a spirit that is steeped in advocacy.”

 

Those of us at CIRM know that passion and advocacy very well. As CIRM Board Chair, Jonathan Thomas, and Vice Chair, Art Torres, said in a joint statement:

“We are delighted that Mayor Lee has chosen Jeff Sheehy to be the new Supervisor. Having worked with Jeff for many years we know that he brings intelligence, dedication and compassion to everything he does. While Jeff is the HIV/AIDS Patient Advocate member on our Board, he has always been a true champion for anyone suffering from an inadequately treated disease, making sure that their voices are heard and reflected in every decision we make. We are confident he will bring those same qualities, and that same passion to the Board of Supervisors. We are also delighted that while he takes on this new role he will still continue to be a member of the CIRM Board and help us fulfill our mission of accelerating stem cell treatments to patients with unmet medical needs.”

As the first HIV-positive person to serve on the Board Jeff said he knows there are going to be tough challenges ahead, for the LGBTQ community and the City, but he said he has one very clear goal:

“This is about the kids, they are our future. If we don’t do well for our kids, we won’t do well for our City.”

He said he is both honored and humbled to be appointed to what he calls “a very challenging job.” But anyone who knows Jeff knows that he never backs away from a challenge.

Scott Weiner, who represented District 8 before being elected to the State Senate, called Jeff “an extraordinary leader, an extraordinary thinker. Some who is tenacious and committed to serving our community.”

Congratulations to Jeff, his husband Billy and their daughter Michelle. That’s a pretty cool way to start 2017.

Key Steps Along the Way To Finding Treatments for HIV on World AIDS Day

Today, December 1st,  is World AIDS Day. It’s a day to acknowledge the progress that is being made in HIV prevention and treatment around the world but also to renew our commitment to a future free of HIV. This year’s theme is Leadership. Commitment. Impact.  At CIRM we are funding a number of projects focused on HIV/AIDS, so we asked Jeff Sheehy, the patient advocate for HIV/AIDS on the CIRM Board to offer his perspective on the fight against the virus.

jeff-sheehy

At CIRM we talk about and hope for cures, but our actual mission is “accelerating stem cell treatments to patients with unmet medical needs.”

For those of us in the HIV/AIDS community, we are tremendously excited about finding a cure for HIV.  We have the example of Timothy Brown, aka the “Berlin Patient”, the only person cured of HIV.

Multiple Shots on Goal

Different approaches to a cure are under investigation with multiple clinical trials.  CIRM is funding three clinical trials using cell/gene therapy in attempts to genetically modify blood forming stem cells to resist infection with HIV.  While we hope this leads to a cure, community activists have come together to urge a look at something short of a “home run.”

A subset of HIV patients go on treatment, control the virus in their blood to the point where it can’t be detected by common diagnostic tests, but never see their crucial immune fighting CD4 T cells return to normal levels after decimation by HIV.

For instance, I have been on antiretroviral therapy since 1997.  My CD4 T cells had dropped precipitously, dangerous close to the level of 200.  At that level, I would have had an AIDS diagnosis and would have been extremely vulnerable to a whole host of opportunistic infections.  Fortunately, my virus was controlled within a few weeks and within a year, my CD T cells had returned to normal levels.

For the immunological non-responders I described above, that doesn’t happen.  So while the virus is under control, their T cell counts remain low and they are very susceptible to opportunistic infections and are at much greater risk of dying.

Immunological non-responders (INRs) are usually patients who had AIDS when they were diagnosed, meaning they presented with very low CD4 T cell counts.  Many are also older.  We had hoped that with frequent testing, treatment upon diagnosis and robust healthcare systems, this population would be less of a factor.  Yet in San Francisco with its very comprehensive and sophisticated testing and treatment protocols, 16% of newly diagnosed patients in 2015 had full blown AIDS.

Until we make greater progress in testing and treating people with HIV, we can expect to see immunological non-responders who will experience sub-optimal health outcomes and who will be more difficult to treat and keep alive.

Boosting the Immune System

A major cell/gene trial for HIV targeted this population.  Their obvious unmet medical need and their greater morbidity/mortality balanced the risks of first in man gene therapy.  Sangamo, a CIRM grantee, used zinc finger nucleases to snip out a receptor, CCR5, on the surface of CD4 T cells taken from INR patients.  That receptor is a door that HIV uses to enter cells.  Some people naturally lack the receptor and usually are unable to be infected with HIV.  The Berlin Patient had his entire immune system replaced with cells from someone lacking CCR5.

Most of the patients in that first trial saw their CD4 T cells rise sharply.  The amount of HIV circulating in their gut decreased.  They experienced a high degree of modification and persistence in T stem cells, which replenish the T cell population.  And most importantly, some who regularly experienced opportunistic infections such as my friend and study participant Matt Sharp who came down with pneumonia every winter, had several healthy seasons.

Missed Opportunities

Unfortunately, the drive for a cure pushed development of the product in a different direction.  This is in large part to regulatory challenges.  A prior trial started in the late 90’s by Chiron tested a cytokine, IL 2, to see if administering it could increase T cells.  It did, but proving that these new T cells did anything was illusive and development ceased.  Another cytokine, IL 7, was moving down the development pathway when the company developing it, Cytheris, ceased business.  The pivotal trial would have required enrolling 4,000 participants, a daunting and expensive prospect.  This was due to the need to demonstrate clinical impact of the new cells in a diverse group of patients.

Given the unmet need, HIV activists have looked at the Sangamo trial, amongst others, and have initiated a dialogue with the FDA.  Activists are exploring seeking orphan drug status since the population of INRs is relatively small.

Charting a New Course

They have also discussed trial designs looking at markers of immune activity and discussed potentially identifying a segment of INRs where clinical efficacy could be shown with far, far fewer participants.

Activists are calling for companies to join them in developing products for INRs.  I’ve included the press release issued yesterday by community advocates below.

With the collaboration of the HIV activist community, this could be a unique opportunity for cell/gene companies to actually get a therapy through the FDA. On this World AIDS Day, let’s consider the value of a solid single that serves patients in need while work continues on the home run.

NEWS RELEASE: HIV Activists Seek to Accelerate Development of Immune Enhancing Therapies for Immunologic Non-Responders.

Dialogues with FDA, scientists and industry encourage consideration of orphan drug designations for therapies to help the immunologic non-responder population and exploration of novel endpoints to reduce the size of efficacy trials.

November 30, 2016 – A coalition of HIV/AIDS activists are calling for renewed attention to HIV-positive people termed immunologic non-responders (INRs), who experience sub-optimal immune system reconstitution despite years of viral load suppression by antiretroviral therapy. Studies have shown that INR patients remain at increased risk of illness and death compared to HIV-positive people who have better restoration of immune function on current drug therapies. Risk factors for becoming an INR include older age and a low CD4 count at the time of treatment initiation. To date, efforts to develop immune enhancing interventions for this population have proven challenging, despite some candidates from small companies showing signs of promise.

“We believe there is an urgent need to find ways to encourage and accelerate development of therapies to reduce the health risks faced by INR patients,” stated Nelson Vergel of the Program for Wellness Restoration (PoWeR), who initiated the activist coalition. “For example, Orphan Drug designations[i] could be granted to encourage faster-track approval of promising therapies.  These interventions may eventually help not only INRs but also people with other immune deficiency conditions”.

Along with funding, a major challenge for approval of any potential therapy is proving its efficacy. While INRs face significantly increased risk of serious morbidities and mortality compared to HIV-positive individuals with more robust immune reconstitution, demonstrating a reduction in the incidence of these outcomes would likely require expensive and lengthy clinical trials involving thousands of individuals. Activists are therefore encouraging the US Food & Drug Administration (FDA), industry and researchers to evaluate potential surrogate markers of efficacy such as relative improvements in clinical problems that may be more frequent in INR patients, such as upper respiratory infections, gastrointestinal disease, and other health issues.

“Given the risks faced by INR patients, every effort should be made to assess whether less burdensome pathways toward approval are feasible, without compromising the regulatory requirement for compelling evidence of safety and efficacy”, said Richard Jefferys of the Treatment Action Group.

The coalition is advocating that scientists, biotech and pharmaceutical companies pursue therapeutic candidates for INRs. For example, while gene and anti-inflammatory therapies for HIV are being assessed in the context of cure research, there is also evidence that they may have potential to promote immune reconstitution and reduce markers associated with risk of morbidity and mortality in INR patients. Therapeutic research should also be accompanied by robust study of the etiology and mechanisms of sub-optimal immune responses.

“While there is, appropriately, a major research focus on curing HIV, we must be alert to evidence that candidate therapies could have benefits for INR patients, and be willing to study them in this context”, argued Matt Sharp, a coalition member and INR who experienced enhanced immune reconstitution and improved health and quality of life after receiving an experimental gene therapy.

The coalition has held an initial conference call with FDA to discuss the issue. Minutes are available online.

The coalition is now aiming to convene a broader dialogue with various drug companies on the development of therapies for INR patients. Stakeholders who are interested in becoming involved are encouraged to contact coalition representatives.

[i] The Orphan Drug Act incentivizes the development of treatments for rare conditions. For more information, see:  http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm

For more information:

Richard Jefferys

Michael Palm Basic Science, Vaccines & Cure Project Director
Treatment Action Group richard.jefferys@treatmentactiongroup.org

Nelson Vergel, Program for Wellness Restoration programforwellness@gmail.com

 

 

Stem cell stories that caught our eye: fashionable stem cells, eliminating HIV, cellular Trojan horse fights cancer

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell fashion for a cause. Science and art are not mutually exclusive subjects. I know plenty of scientists who are talented painters or designers. But you don’t often see science being displayed in an artistic way or art being used to help explain complex scientific topics. I think that in the future, this will change as both subjects have a lot to offer one another.

Stem cell ties are in fashion!

Stem cell ties are in fashion!

Take this story from the University of Michigan for instance. Designer Dominic Pangborn has joined forces with the Heinz C. Prechter Bipolar Research Fund at the University of Michigan (UOM) to design fashionable scarves and ties featuring beautiful pictures of stem cells. The goal of the Prechter Fund scarf and tie project is to raise awareness for mental health research.

The scarves and ties feature pictures of brain stem cells taken by UOM scientists who are studying them to understand the mechanisms behind bipolar disorder. These stem cells were generated from induced pluripotent stem cells or iPS cells that were derived from donated skin biopsies of patients with bipolar disease. Studying these diseased brain cells in a dish revealed that the nerve cells from bipolar patients were misbehaving, sending out electrical signals more frequently compared to healthy nerve cells.

Dr. Melvin McInnis, the Prechter Fund research director, explained:

“By understanding the causes of bipolar disorder, we will be able to develop new treatments for the illness and most importantly, we’ll be able to prevent destructive mood episodes. Our ultimate goal is to allow people to live happy, normal lives.”

Pangborn is passionate about using art to reflect an important cause.

“I decided to add butterflies to the design because they signify metamorphosis. Our society is finally at a point where mental illness is openly talked about and research is taking a turn for the better.”

He plans to release his collection in time for National Mental Health Awareness month in May. All proceeds will go to the Prechter bipolar research projects at UOM.

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

New stem cell therapy could eliminate HIV for good

The stem cells therapies being developed to cure HIV are looking more promising every day. A few are already being tested in clinical trials, and CIRM is funding two of them (you can read more about them here). News came out this week about a new trial conducted at the City of Hope’s CIRM Alpha Stem Cell Clinic. They reported in a news release that they’ve treated their first patient. His name is Aaron Kim, and he’s had HIV since he was born. In 1983, he and his twin sister were born prematurely and due to a complication, Aaron had to get a blood transfusion that unfortunately gave him HIV.

Aaron Kim with nurse. (City of Hope)

Aaron Kim with nurse. (City of Hope)

Aaron thought he would live with this disease the rest of his life, but now he has a chance at being cured. In March, Aaron received a transplant of his own bone marrow stem cells that were genetically engineered to have a modified version of the CCR5 gene that makes his cells resistant to HIV infection. CCR5 is a is a protein receptor on the surface of blood cells that acts as a gateway for HIV entry. The hope is that his reengineered stem cells will populate his immune system with HIV-resistant cells that can eliminate the virus completely.

Dr. John Zaia who is the director the the City of Hope Alpha Clinic explained,

“The stem cell therapy Aaron received is one of more than 20 cure strategies for HIV. It may not cure him, but our goal is to reduce or even halt Aaron’s reliance on HIV drugs, potentially eliminating the virus completely.”

My favorite part of this story was that it acknowledged how importance it is for patients to participate in clinical trials testing promising new stem cell therapies where the outcomes aren’t always known. Brave patients such as Aaron make it possible for scientists to make progress and develop better and safer treatments for patients in the future.

Dr. Zaia commented, “It’s a wonderful and generous humanitarian gesture on Aaron’s part to participate in this trial.”

Stem cell Trojan horse fights cancer

Chemotherapy is great at killing cancer cells, but unfortunately, it’s also great at killing healthy cells too. To combat this issue, scientists are developing new delivery methods that can bring high doses of chemotherapy drugs to the cancer tumors and minimize exposure of healthy tissues.

Mesenchymal stem cells loaded with drug-containing microparticles. Credit: Jeff Karp and Oren Levy, Brigham and Women's Hospital

Mesenchymal stem cells loaded with drug-containing microparticles.
Credit: Jeff Karp and Oren Levy, Brigham and Women’s Hospital

A study published this week in Biomaterials, describes a new drug delivery method that has the potential to be an effective treatment for prostate cancer. Researchers from the Brigham and Women’s Hospital and Johns Hopkins University developed a drug delivery platform using mesenchymal stem cells. They packaged a non-active, prodrug version of a potent prostate cancer chemotherapy drug into microparticles that they loaded into MSCs. When the MSCs and prostate cancer cells were cultured together in a dish, the MSCs released their prodrug cargo, which was then internalized by the prostate cancer cells. The prodrug was then metabolized into its active, cancer-killing form and was very effective at killing the cancer cells.

In a news release picked up by Science Daily, one of the lead scientists on the study, Dr. Oren Levy, further explained the stem cell Trojan horse concept:

“Mesenchymal stem cells represent a potential vehicle that can be engineered to seek out tumors. Loading those cells with a potent chemotherapeutic drug is a promising cell-based Trojan horse approach to deliver drugs to sites of cancer.”

If all goes well, the teams plan to develop different versions of their stem cell-based drug delivery method that target different cancers and other diseases.

HIV/AIDS: Progress and Promise of Stem Cell Research

Our friends at Americans for Cures and Youreka Science have done it again. They’ve produced another whiteboard video about the progress and promise of stem cell research that’s so inspiring that it would probably make Darth Vader consider coming back to the light side. This time they tackled HIV.

If you haven’t watched one of these videos already, let me bring you up to speed. Americans for Cures is a non-profit organization, the legacy of the passing of Proposition 71, that supports patient advocates in the fight for stem cell research and cures. They’ve partnered with Youreka Science to produce eye-catching and informative videos to teach patients and the general public about the current state of stem cell research and the quest for cures for major diseases.

Stem cell cure for HIV?

Their latest video is on HIV, a well-known and deadly virus that attacks and disables the human immune system. Currently, 37 million people globally are living with HIV and only a few have been cured.

The video begins with the story of Timothy Brown, also known as the Berlin patient. In 2008 at the age of 40, he was dying of a blood cancer called acute myeloid leukemia and needed a bone marrow stem cell transplant to survive. Timothy was also HIV positive, so his doctor decided to use a bone marrow donor who happened to be naturally resistant to HIV infection. The transplanted donor stem cells were not only successful in curing Timothy of his cancer, but they also “rebooted his immune system” and cured his HIV.

Screen Shot 2015-12-23 at 2.21.18 PMSo why haven’t all HIV patients received this treatment? The video goes on to explain that bone marrow transplants are dangerous and only used in cancer patients who’ve run out of options. Additionally, only a small percentage of the world’s population is resistant to HIV and the chances that one of these individuals is a bone marrow donor match to a patient is very low.

This is where science comes to the rescue. Three research groups in California, all currently supported by CIRM funding, have proposed alternative solutions: they are attempting to make a patient’s own immune system resistant to HIV instead of relying on donor stem cells. Using gene therapy, they are modifying blood stem cells from HIV patients to be HIV resistant, and then transplanting the modified stem cells back into the same patient to rebuild a new immune system that can block HIV infection.

Screen Shot 2015-12-23 at 4.47.17 PM

All three groups have proven their stem cell technology works in animals; two of them are now testing their approach in early phase clinical trials in humans, and one is getting ready to do so. If these trials are successful, there is good reason to hope for an HIV cure and maybe even cures for other immune diseases.

My thoughts…

What I liked most about this video was the very end. It concludes by saying that these accomplishments were made possible not just by funding promising scientific research, but also by the hard work of HIV patients and patient advocate communities, who’ve brought awareness to the disease and influenced policy changes. Ultimately, a cure for HIV will depend on researchers and patient advocates working together to push the pace and to tackle any obstacles that will likely appear with testing stem cell therapies in human clinical trials.

I couldn’t say it any better than the final line of the video:

“We must remember that human trials will celebrate successes, but barriers will surface along with complications and challenges. So patience and understanding of the scientific process are essential.”

Stem cell stories that caught our eye: cancer fighting virus, lab-grown guts work in dogs, stem cell trial to cure HIV

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Cancer fighting virus approved for melanoma

(Disclaimer: While this isn’t a story about stem cells, it’s pretty cool so I had to include it.)

The term “virus” generally carries a negative connotation, but in some cases, viruses can be the good guys. This was the case on Tuesday when our drug approval agency, the US Food and Drug Administration (FDA), approved the use of a cancer fighting virus for the treatment of advanced stage melanoma (skin cancer).

The virus, called T-VEC, is a modified version of the herpesvirus, which causes a number of diseases and symptoms including painful blisters and sores in the mouth. Scientists engineered this virus to specifically infect cancer cells and not healthy cells. Once inside cancer cells, T-VEC does what a virus normally does and wreaks havoc by attacking and killing the tumor.

The beauty of this T-VEC is that in the process of killing cancer cells, it causes the release of a factor called GM-CSF from the cancer cells. This factor signals the human immune system that other cancer cells are nearby and they should be attacked and killed by the soldiers of the immune system known as T-cells. The reason why cancers are so deadly is because they can trick the immune system into not recognizing them as bad guys. T-VEC rips off their usual disguise and makes them vulnerable again to attack.

T-VEC recruits immune cells (orange) to attack cancer cells (pink) credit Dr. Andrejs Liepins/SPL

T-VEC recruits immune cells (orange) to attack cancer cells (pink). Photo credit Dr. Andrejs Liepins/SPL.

This is exciting news for cancer patients and was covered in many news outlets. Nature News wrote a great article, which included the history of how we came to use viruses as tools to attack cancer. The piece also discussed options for improving current T-VEC therapy. Currently, the virus is injected directly into the cancer tumor, but scientists hope that one day, it could be delivered intravenously, or through the bloodstream, so that it can kill hard to reach tumors or ones that have spread to other parts of the body. The article suggested combining T-VEC with other cancer immunotherapies (therapies that help the immune system recognize cancer cells) or delivering a personalized “menu” of cancer-killing viruses to treat patients with different types of cancers.

As a side note, CIRM is also interested in fighting advanced stage melanoma and recently awarded $17.7 million to Caladrius Biosciences to conduct a Phase 3 clinical trial with their melanoma killing vaccine. For more, check out our recent blog.

Lab-grown guts work in mice and dogs

If you ask what’s trending right now in stem cell research, one of the topics that surely would pop up is 3D organoids. Also known as “mini-organs”, organoids are tiny models of human organs generated from human stem cells in a dish. To make them, scientists have developed detailed protocols that sometimes involve the use of biological scaffolds (structures on which cells can attach and grow).

A study published in Regenerative Medicine and picked up by Science described the generation of “lab-grown gut” organoids using intestine-shaped scaffolds. Scientists from Johns Hopkins figured out how to grow intestinal lining that had the correct anatomy and functioned properly when transplanted into mice and dogs. Previous studies in this area used flat scaffolds or dishes to grow gut organoids, which weren’t able to form proper functional gut lining.

Lab-grown guts could help humans with gut disorders. (Shaffiey et al., 2015)

Lab-grown guts could help humans with gut disorders. (Shaffiey et al., 2015)

What was their secret recipe? The scientists took stem cells from the intestines of human infants or mice and poured a sticky solution of them onto a scaffold made of suture-like material. The stem cells then grew into healthy gut tissue over the next few weeks and formed tube structures that were similar to real intestines.

They tested whether their mini-guts worked by transplanting them into mice and dogs. To their excitement, the human and mouse lab-grown guts were well tolerated and worked properly in mice, and in dogs that had a portion of their intestine removed. Even more exciting was an observation made by senior author David Hackham:

“The scaffold was well tolerated and promoted healing by recruiting stem cells. [The dogs] had a perfectly normal lining after 8 weeks.”

The obvious question about this study is whether these lab-grown guts will one day help humans with debilitating intestinal diseases like Crohn’s and IBS (inflammatory bowel disorder). Hackam said that while they are still a long way from taking their technology to the clinic, “in the future, scaffolds could be custom-designed for individual human patients to replace a portion of an intestine or the entire organ.”

Clinical trial using umbilical cord stem cells to treat HIV

This week, the first clinical trial using human umbilical cord stem cells to treat HIV patients was announced in Spain. The motivation of this trial is the previous success of the Berlin Patient, Timothy Brown.

The Berlin patient can be described as the holy grail of HIV research. He is an American man who suffered from leukemia, a type of blood cancer, but was also HIV-positive. When his doctor in Berlin treated his leukemia with a stem cell transplant from a bone-marrow donor, he chose a special donor whose stem cells had an inherited mutation in their DNA that made them resistant to infection by the HIV virus. Surprisingly, after the procedure, Timothy was cured of both his cancer AND his HIV infection.

Berlin patient Timothy Brown. Photo credit: Griffin Boyce/Flickr.

Berlin patient Timothy Brown. Photo credit: Griffin Boyce/Flickr.

The National Organization of Transplants (ONT) in Spain references this discovery as its impetus to conduct a stem cell clinical trial to treat patients with HIV and hopefully cure them of this deadly virus. The trial will use umbilical cord blood stem cells instead of bone-marrow stem cells from 157 blood donors that have the special HIV-resistance genetic mutation.

In coverage from Tech Times, the president of the Spanish Society of Hematology and Hemotherapy, Jose Moraleda, was quoted saying:

“This project can put us at the cutting edge of this field within the world of science. It will allow us to gain more knowledge about HIV and parallel offer us a potential option for curing a poorly diagnosed malignant hematological disease.”

The announcement for the clinical trial was made at the Haematology conference in Valencia, and ONT hopes to treat its first patient in December or January.

Calling for a cure for HIV/AIDS

Larry Kramer - Photo by David Shankbone

Larry Kramer – Photo by David Shankbone

Larry Kramer is a pivotal figure in the history of HIV/AIDS. His activism on many fronts has been widely credited with changing public health policy and speeding up access to experimental medications for people infected with the virus. So when he says that the fight for treatment is not enough but “The battle cry now must be one word — cure, cure, cure!” People pay attention.

A few years ago it might have been considered dangerously optimistic to use the word “cure” in any conversation about HIV/AIDS, but that’s no longer the case. In fact cure is something that is becoming not just a wildly ambitious dream, but something that scientists are working hard to achieve right now.

On Tuesday, October 6th, we are going to hold an HIV/AIDS Cure Town Hall meeting in Palm Springs. This will be the third event we’ve held and the previous two, in San Francisco and Los Angeles, were hugely successful. It’s not hard to understand why. Our experts are going to be talking about their work in trying to eradicate the AIDS virus from people infected with it.

This includes clinical trials run by Calimmune and City of Hope/Sangamo, plus some truly cutting edge research by Dr. Paula Cannon of the University of Southern California.

The clinical trials are both taking similar, if slightly different, approaches to reach the same goal; functionally curing people with HIV. They take the patient’s own blood stem cells and genetically modify them so that the AIDS virus is no longer able to infect them. They also help boost the patient’s T cells, a key part of a healthy immune system and the virus’ main target, so that they can fight back against the virus. It’s a kind of one-two punch to block and eventually evict the virus.

Timothy Brown; photo courtesy CureAIDSreport.org

Timothy Brown; photo courtesy CureAIDSreport.org

This work is based on the real-life experiences of Timothy Ray Brown, the “Berlin Patient”. He became the first person ever cured of HIV/AIDS when he got a bone marrow transplant from a person with a natural resistance to HIV. This created a new blood supply and a new immune system both of which were resistant to HIV.

Timothy is going to be joining us at the event in Palm Springs to share his story and show that cure is not just a word it’s a goal; one that we can now think of as being possible.

The HIV/AIDS Cure Town Hall event will be held on Tuesday, October 6th in the Sinatra Auditorium at the Desert Regional Medical Center in Palm Springs. Doors open at 6pm and the program starts at 6.30pm. And of course, it’s free.

Stem cell stories that caught our eye: Immune therapy for HIV, nerves grown on diamonds and how stem cells talk

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Trendy CAR T therapy tried on HIV.  The hottest trend in cancer therapy today is using CAR-T cells to attack and rid the body of cancer. Technically called chimeric antigen receptors the technology basically provides our own immune system with directions to cancer cells and keys to get inside them and destroy them. A CIRM-funded team at the University of California, Los Angeles, has now tried that same scheme with HIV.

Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent.

Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent.

The researchers worked with mice bred to have a human immune system so that HIV affects them similarly to humans. They harvested their blood-forming stem cells and inserted a CAR that recognized HIV. After giving the stem cells back to the mice they produced T cells capable of seeking out and destroying about 90 percent of the virus. The technique has a ways to go, but the study’s lead author noted their ultimate goal in a University press release picked up by HealthCanal:

“We hope this approach could one day allow HIV-positive individuals to reduce or even stop their current HIV drug regimen and clear the virus from the body altogether,” said Scott Kitchen. “We also think this approach could possibly be extended to other diseases.”

Nerves grown on diamonds. Diamonds are so chemically non-reactive our bodies would not recognize them as foreign. But they can also be made to conduct electricity, which could make nerves grown on their surface able to be turned on and off with electrical impulses. When developing cell therapy for several neurologic diseases the ability to control the activity of replacement cells could be critical to success—making new research by a team in Britain and Ireland intriguing, if very preliminary.

They doped diamonds with boron to make them able to conduct electricity and then used them as a surface for growing nerve stem cells that could later be turned into nerves. They then succeeded in growing nerves long term on the diamonds.

“We still have a lot more fundamental studies of the neuron/diamond interface to perform,” said Paul May of the University of Bristol. “[But] the long term possibilities for this work are exciting.  Long-lifetime diamond bio-implants may offer treatments for Parkinson’s, Alzheimer’s, stroke or even epilepsy.”

Materials Today wrote a piece explaining the work.

Some stem cells talk over “land lines.” Most cellular communication works through chemical signals that get dispatched by one cell and received by others. It turns out that some types of stem cells communicate by sending out tiny nanotubes, sort of a cellular land line.

A team at the University of Michigan and the University of Texas Southwestern Medical Center found the new form of communication working with fruit flies. Yukiko Yamashita, a senior author of the paper from Michigan explained why it is so important to get a better understanding of cell-to-cell communication in a university press release picked up by ScienceNewsline:

“There are trillions of cells in the human body, but nowhere near that number of signaling pathways. There’s a lot we don’t know about how the right cells get just the right messages to the right recipients at the right time.”

In a classic example of the beauty of young minds in science, prior images of these stem cells had shown the nanotubes, but they had been overlooked until a graduate student asked what they were.

Phase 3 melanoma trial explained. When a new therapy gets into its third and final phase of testing it is make or break for the company developing the therapy and for patients who hope it will become broadly available. CIRM recently provided funding to our first phase three clinical trial, one aimed at metastatic melanoma being conducted by Caladrius Biosciences.

The CEO of the company, David Mazzo, gave an interview with The New Economy this week that does a nice job of explaining the goal of the therapy and how it is different from other therapies currently used or being developed. The therapy’s main difference is its ability to target the cancer-inducing cells thought to responsible for the spread of the disease.