Stem Cell RoundUp: CIRM Clinical Trial Updates & Mapping Human Brain

It was a very CIRMy news week on both the clinical trial and discovery research fronts. Here are some the highlights:

Stanford cancer-fighting spinout to Genentech: ‘Don’t eat me’San Francisco Business Times

Ron Leuty, of the San Francisco Business Times, reported this week on not one, but two news releases from CIRM grantee Forty Seven, Inc. The company, which originated from discoveries made in the Stanford University lab of Irv Weissman, partnered with Genentech and Merck KGaA to launch clinical trials testing their drug, Hu5F9-G4, in combination with cancer immunotherapies. The drug is a protein antibody that blocks a “don’t eat me” signal that cancer stem cells hijack into order to evade destruction by a cancer patient’s immune system.

Genentech will sponsor two clinical trials using its FDA-approved cancer drug, atezolizumab (TECENTRIQ®), in combination with Forty Seven, Inc’s product in patients with acute myeloid leukemia (AML) and bladder cancer. CIRM has invested $5 million in another Phase 1 trial testing Hu5F9-G4 in AML patients. Merck KGaA will test a combination treatment of its drug avelumab, or Bavencio, with Forty-Seven’s Hu5F9-G4 in ovarian cancer patients.


Novel regenerative drug for osteoarthritis entering clinical trialsThe Scripps Research Institute

The California Institute for Biomedical Research (Calibr), a nonprofit affiliate of The Scripps Research Institute, announced on Tuesday that its CIRM-funded trial for the treatment of osteoarthritis will start treating patients in March. The trial is testing a drug called KA34 which prompts adult stem cells in joints to specialize into cartilage-producing cells. It’s hoped that therapy will regenerate the cartilage that’s lost in OA, a degenerative joint disease that causes the cartilage that cushions joints to break down, leading to debilitating pain, stiffness and swelling. This news is particularly gratifying for CIRM because we helped fund the early, preclinical stage research that led to the US Food and Drug Administration’s go-ahead for this current trial which is supported by a $8.4 million investment from CIRM.


And finally, for our Cool Stem Cell Image of the Week….

Genetic ‘switches’ behind human brain evolutionScience Daily

180111115351_1_540x360

This artsy scientific imagery was produced by UCLA researcher Luis del la Torre-Ubieta, the first author of a CIRM-funded studied published this week in the journal, Cell. The image shows slices of the mouse (bottom middle), macaque monkey (center middle), and human (top middle) brain to scale.

The dramatic differences in brain size highlights what sets us humans apart from those animals: our very large cerebral cortex, a region of the brain responsible for thinking and complex communication. Torre-Ubieta and colleagues in Dr. Daniel Geschwind’s laboratory for the first time mapped out the genetic on/off switches that regulate the growth of our brains. Their results reveal, among other things, that psychiatric disorders like schizophrenia, depression and Attention-Deficit/Hyperactivity Disorder (ADHD) have their origins in gene activity occurring in the very earliest stages of brain development in the fetus. The swirling strings running diagonally across the brain slices in the image depict DNA structures, called chromatin, that play a direct role in the genetic on/off switches.

Advertisements

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 Board invests in three new stem cell clinical trials targeting arthritis, cancer and deadly infections

knee

Arthritis of the knee

Every day at CIRM we get calls from people looking for a stem cell therapy to help them fight a life-threatening or life-altering disease or condition. One of the most common calls is about osteoarthritis, a painful condition where the cartilage that helps cushion our joints is worn away, leaving bone to rub on bone. People call asking if we have something, anything, that might be able to help them. Now we do.

At yesterday’s CIRM Board meeting the Independent Citizens’ Oversight Committee or ICOC (the formal title of the Board) awarded almost $8.5 million to the California Institute for Biomedical Research (CALIBR) to test a drug that appears to help the body regenerate cartilage. In preclinical tests the drug, KA34, stimulated mesenchymal stem cells to turn into chondrocytes, the kind of cell found in healthy cartilage. It’s hoped these new cells will replace those killed off by osteoarthritis and repair the damage.

This is a Phase 1 clinical trial where the goal is primarily to make sure this approach is safe in patients. If the treatment also shows hints it’s working – and of course we hope it will – that’s a bonus which will need to be confirmed in later stage, and larger, clinical trials.

From a purely selfish perspective, it will be nice for us to be able to tell callers that we do have a clinical trial underway and are hopeful it could lead to an effective treatment. Right now the only alternatives for many patients are powerful opioids and pain killers, surgery, or turning to clinics that offer unproven stem cell therapies.

Targeting immune system cancer

The CIRM Board also awarded Poseida Therapeutics $19.8 million to target multiple myeloma, using the patient’s own genetically re-engineered stem cells. Multiple myeloma is caused when plasma cells, which are a type of white blood cell found in the bone marrow and are a key part of our immune system, turn cancerous and grow out of control.

As Dr. Maria Millan, CIRM’s President & CEO, said in a news release:

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells.  Less than half of patients with multiple myeloma live beyond 5 years. Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

In a news release from Poseida, CEO Dr. Eric Ostertag, said the therapy – called P-BCMA-101 – holds a lot of promise:

“P-BCMA-101 is elegantly designed with several key characteristics, including an exceptionally high concentration of stem cell memory T cells which has the potential to significantly improve durability of response to treatment.”

Deadly infections

The third clinical trial funded by the Board yesterday also uses T cells. Researchers at Children’s Hospital of Los Angeles were awarded $4.8 million for a Phase 1 clinical trial targeting potentially deadly infections in people who have a weakened immune system.

Viruses such as cytomegalovirus, Epstein-Barr, and adenovirus are commonly found in all of us, but our bodies are usually able to easily fight them off. However, patients with weakened immune systems resulting from chemotherapy, bone marrow or cord blood transplant often lack that ability to combat these viruses and it can prove fatal.

The researchers are taking T cells from healthy donors that have been genetically matched to the patient’s immune system and engineered to fight these viruses. The cells are then transplanted into the patient and will hopefully help boost their immune system’s ability to fight the virus and provide long-term protection.

Whenever you can tell someone who calls you, desperately looking for help, that you have something that might be able to help them, you can hear the relief on the other end of the line. Of course, we explain that these are only early-stage clinical trials and that we don’t know if they’ll work. But for someone who up until that point felt they had no options and, often, no hope, it’s welcome and encouraging news that progress is being made.