CD47

Early CIRM support helps stem cell pioneer develop promising new therapy for cancer

/ Kevin McCormack / Leave a comment
Irv Weissman

Irv Weissman, Ph.D., Photo: courtesy Stanford University

When you get praise from someone who has been elected to the National Academy of Sciences and has been named California Scientist of the Year you know you must be doing something right.

That’s how we felt the other day when Irv Weissman, Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, issued a statement about how important the support of CIRM was in advancing his research.

The context was the recent initial public offering (IPO) of Forty Seven Inc.. a company co-founded by Dr. Weissman. That IPO followed news that two Phase 2 clinical trials being run by Forty Seven Inc. were demonstrating promising results against hard-to-treat cancers.

Dr. Weissman says the therapies used a combination of two monoclonal antibodies, 5F9 from Forty Seven Inc. and Rituximab (an already FDA-approved treatment for cancer and rheumatoid arthritis) which:

“Led to about a 50% overall remission rate when used on patients who had relapsed, multi-site disease refractory to rituximab-plus-chemotherapy. Most of those patients have shown a complete remission, although it’s too early to tell if this is complete for life.”

5F9 attacks a molecule called CD47 that appears on the surface of cancer cells. Dr. Weissman calls CD47 a “don’t eat me signal” that protects the cancer against the body’s own immune system. By blocking the action of CD47, 5F9 strips away that “don’t eat me signal” leaving the cancer vulnerable to the patient’s immune system. We have blogged about this work here and here.

The news from these trials is encouraging. But what was gratifying about Dr. Weissman’s statement is his generosity in sharing credit for the work with CIRM.

Here is what he wrote:

“What is unusual about Forty Seven is that not only the discovery, but its entire preclinical development and testing of toxicity, etc. as well as filing two Investigational New Drug [IND] applications to the Food and Drug Administration (FDA) in the US and to the MHRA in the UK, as well as much of the Phase 1 trials were carried out by a Stanford team led by two of the discoverers, Ravi Majeti and Irving Weissman at Stanford, and not at a company.

The major support came from the California Institute of Regenerative Medicine [CIRM], funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.

This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”

Dr. Weissman also had praise for CIRM’s funding model which requires companies that produce successful, profitable therapies – thanks to CIRM support – to return a portion of those profits to California. Most other funding agencies don’t have those requirements.

“US federal funds, from agencies such as the National Institutes of Health (NIH) similarly support discovery but cannot fund more than a few projects to, and through, early phase clinical trials. And, under the Bayh-Dole Act, the universities keep all of the equity and royalties derived from licensing discoveries. In that model no money flows back to the agency (or the public), and nearly a decade of level or less than level funding (at the national level) has severely reduced academic research. So this experiment of funding (the NIH or the CIRM model) is now entering into the phase that the public will find out which model is best for bringing new discoveries and new companies to the US and its research and clinical trials community.”

We have been funding Dr. Weissman’s work since 2006. In fact, he was one of the first recipients of CIRM funding.  It’s starting to look like a very good investment indeed.

 

Seeing is believing. Proof a CIRM-funded therapy is making a difference

/ Kevin McCormack / Leave a comment
ThelmaScreenShotFB

Thelma, participant in the CAMELLIA clinical trial

You have almost certainly never heard of Thelma, or met her, or know anything about her. She’s a lady living in England who, if it wasn’t for a CIRM-funded therapy, might not be living at all. She’s proof that what we do, is helping people.

Thelma is featured in a video about a treatment for acute myeloid leukemia, one of the most severe forms of blood cancer. Thelma took part in a clinical trial, called CAMELLIA, at Oxford Cancer Centre in Oxford, UK. The clinical trial uses a therapy that blocks a protein called CD47 that is found on the surface of cancer cells, including cancer stem cells which can evade traditional therapies. The video was shot to thank the charity Bloodwise for raising the funds to pay for the trial.

Prof. Paresh Vyas of Oxford University, who was part of the clinical trial team that treated Thelma, says patients with this condition face long odds.

“Patients with acute myeloid leukemia have the most aggressive blood cancer. We really haven’t had good treatments for this condition for the last 40 years.”

While this video was shot in England, featuring English nurses and doctors and patients, the therapy itself was developed here in California, first at Stanford University under the guidance of Irv Weissman and, more recently, at Forty Seven Inc. That company is now about to test their approach in a CIRM-funded clinical trial here in the US.

This is an example of how CIRM doesn’t just fund research, we invest in it. We help support it at every stage, from the earliest research through to clinical trials. Without our early support this work may not have made it this far.

The Forty Seven Inc. therapy uses the patient’s own immune system to help fight back against cancer stem cells. It’s looking very promising. But you don’t have to take our word for it. Take Thelma’s.

How Tom Howing turned to stem cells to battle back against a deadly cancer

/ Kevin McCormack / 2 Comments

As we enter the new year, CIRM’s 2017 Annual Report will be posted in less than two weeks!  Here’s one of the people we are profiling in the report, a patient who took part in a CIRM-funded clinical trial.

Tom Howing

In March of 2015, Tom Howing was diagnosed with stage 4 cancer. Over the next 18 months, he underwent two rounds of surgery and chemotherapy. Each time the treatments held the cancer at bay for a while. But each time the cancer returned. Tom was running out of options and hope when he heard about a CIRM-funded clinical trial using a new approach.

The clinical trial uses a therapy that blocks a protein called CD47 that is found on the surface of cancer cells, including cancer stem cells which can evade traditional therapies. CD47 acts as a ‘don’t eat me’ signal that tells immune cells not to kill off the cancer cells. When this ‘don’t eat me’ signal is blocked by the antibody, the patient’s immune system is able to identify, target and kill the cancer stem cells.

“When I was diagnosed with cancer I knew I had battle ahead of me. After the cancer came back again they recommended I try this CD47 clinical trial. I said absolutely, let’s give it a spin.

“I guess one is always a bit concerned whenever you put the adjective “experimental” in front of anything. But I’ve always been a very optimistic and positive person and have great trust and faith in my caregivers.

“Whenever you are dealing with a Phase 1 clinical trial (the earliest stage where the goal is first to make sure it is safe), there are lots of unknowns.  Scans and blood tests came back showing that the cancer appears to be held in check. My energy level is fantastic. The treatment that I had is so much less aggressive than chemo, my quality of life is just outstanding.”

Tom says he feels fortunate to be part of the clinical trial because it is helping advance research, and could ultimately help many others like him.

“The most important thing I would say is, I want people to know there is always hope and to stay positive.”

He says he feels grateful to the people of California who created CIRM and the funding behind this project: “I say a very heartfelt thank you, that this was a good investment and a good use of public funds.”

He also wants the researchers, who spent many years developing this approach, to know that they are making a difference.

“To all those people who are putting in all the hours at the bench and microscope, it’s important for them to know that they are making a huge impact on the lives of real people and they should celebrate it and revel in it and take great pride in it.”

Second “Don’t Eat Me” Signal Identified in Cancer Cells, Points to New Immunotherapies

/ Todd Dubnicoff / 1 Comment

When the immune system comes up as a topic in everyday conversation, it’s usually related to fighting off a cold or flu. While our immune cells certainly do detect and neutralize invading bacteria and viruses, they also play a critical role in killing abnormal, cancerous cells from within our bodies.

“Don’t Eat Me” Signal 101
A white blood cell called a macrophage (macro = “big”; phage = “eater”) is part of the so-called innate immune system and acts as a first line of defense by patrolling our organs and gobbling up infected as well as cancerous cells (see macrophages in action in the cool video below).

Unfortunately, cancer cells possess the ability to cloak themselves and escape a macrophage’s engulfing grasp. Nearly all cancer cells carry a protein called CD47 on their surface. When CD47 binds to a protein called SIRPalpha on the surface of macrophages, a “don’t eat me” signal is triggered and the macrophage ignores the cancer cell.

Stanford researcher Irv Weissman and his team discovered this “don’t eat me” signal several years ago and showed that adding an antibody protein that binds tightly to CD47 interferes with the CD47/SIRPalpha signal. As a result, the anti-CD47 antibody deactivates the cancer cell’s “don’t eat me” signal and restores the macrophage’s ability to detect and kill the cancer cells.

cd47-gene3

CD47 protein on surface of cancer cells triggers “don’t eat me signal” which can be blocked with anti-CD47 antibody. Image: Acrobiosystems

Because CD47 is found on the surface of most cancer cells, this anti-CD47 antibody represents an exciting new strategy for targeting cancer stem cells – the cells thought to maintain cancer growth and cause tumor relapse – in a wide variety of cancers. In fact, CIRM has provided funding for three clinical trials, one sponsored by Stanford University and two by Forty-Seven Inc. (a company that was spun out of Stanford), that are testing anti-CD47 therapy for the treatment of the blood cancer acute myeloid leukemia (AML), as well as colon cancer and other solid tumors.

“Reaching Clinical Trials” does not equal “The Research is Done”
Although these clinical trials are underway, the Weissman team continues to seek new insights related to blocking the CD47 “don’t eat me” signal. They observed that although anti-CD47 led to increased macrophage-induced killing of most cancer cell samples tested, some were resistant to anti-CD47 and remained cloaked from macrophages. And even the cancer cells that did respond to the antibody varied widely in the amount of increased killing by macrophages.

These results suggested that alternate processes may exist that allow some cancers to evade macrophages even when the CD47 “don’t eat me” signal is blocked. In a report published this week in Nature Immunology, the researchers report the identification of a second, independent “don’t eat me” signal, which may lead to more precise methods to disarm a cancer’s evasiveness.

To track down this alternate “don’t eat me” signal, they looked for, but didn’t find, correlations between specific types of cancer cells and the cancer’s resistance to anti-CD47 treatment.  So instead they analyzed surface proteins found on the various cancer cell samples and found that cancer cells that had high levels of MHC (Major Histocompatibility Complex) class I proteins were more likely to be resistant to anti-CD47 antibodies.

A Second “Don’t Eat Me” Signal
MHC class I proteins help another arm of the immune system, the adaptive immune response, detect what’s going inside a cell. They are found on nearly all cells and display, at the cell surface, bits of proteins sampled from inside the cell. If cells of the adaptive immune response, such as T or B cells, recognize one of those protein bits as abnormal or foreign, efficient killing mechanisms are kicked into high gear to destroy those cells.

But in the case of cancers cells, the MHC class I protein are harnessed as a “don’t eat me” signal by binding to a protein called LILRB1 on macrophages. When either the MHC class I proteins or LILRB1 were blocked, the “don’t eat me” signal was lifted and restored the macrophages’ ability to kill the cancer cells both in petri dish samples as well as in mice that carried human cancers.

Graduate student and co-lead author Amira Barkal described in a press release the impact of blocking both “don’t eat me” signals at the same time:

barkalSm

Amira Barkal

“Simultaneously blocking both these pathways in mice resulted in the infiltration of the tumor with many types of immune cells and significantly promoted tumor clearance, resulting in smaller tumors overall. We are excited about the possibility of a double- or perhaps even triple-pronged therapy in humans in which we combine multiple blockades to cancer growth.”

The Big Picture for Cancer Immunotherapies
Because MHC protein class I proteins play an important role in stimulating immune cells called T cells to kill cancer cells as part of the adaptive immune response, the level of MHC protein on an individual patient’s cancer cells could serve as an indicator, or “biomarker”, for what type of cancer therapy to pursue.  The big picture implications of this idea are captured in the press release:

“Understanding the balance between adaptive and innate immunity is important in cancer immunotherapy. For example, it’s not uncommon for human cancer cells to reduce the levels of MHC class 1 on their surfaces to escape destruction by T cells. People with these types of tumors may be poor candidates for cancer immunotherapies meant to stimulate T cell activity against the cancer. But these cells may then be particularly vulnerable to anti-CD47 treatment, the researchers believe. Conversely, cancer cells with robust MHC class 1 on their surfaces may be less susceptible to anti-CD47.”

Curing the Incurable through Definitive Medicine

/ Karen Ring / 1 Comment

“Curing the Incurable”. That was the theme for the first annual Center for Definitive and Curative Medicine (CDCM) Symposium held last week at Stanford University, in Palo Alto, California.

The CDCM is a joint initiative amongst Stanford Healthcare, Stanford Children’s Health and the Stanford School of Medicine. Its mission is to foster an environment that accelerates the development and translation of cell and gene therapies into clinical trials.

The research symposium focused on “the exciting first-in-human cell and gene therapies currently under development at Stanford in bone marrow, skin, cardiac, neural, pancreatic and neoplastic diseases.” These talks were organized into four different sessions: cell therapies for neurological disorders, stem cell-derived tissue replacement therapies, genome-edited cell therapies and anti-cancer cell-based therapies.

A few of the symposium speakers are CIRM-funded grantees, and we’ll briefly touch on their talks below.

Targeting cancer

The keynote speaker was Irv Weissman, who talked about hematopoietic or blood-forming stem cells and their value as a cell therapy for patients with blood disorders and cancer. One of the projects he discussed is a molecule called CD47 that is found on the surface of cancer cells. He explained that CD47 appears on all types of cancer cells more abundantly than on normal cells and is a promising therapeutic target for cancer.

Irv Weissman

Irv Weissman

“CD47 is the first gene whose overexpression is common to all cancer. We know it’s molecular mechanism from which we can develop targeted therapies. This would be impossible without collaborations between clinicians and scientists.”

 

At the end of his talk, Weissman acknowledged the importance of CIRM’s funding for advancing an antibody therapeutic targeting CD47 into a clinical trial for solid cancer tumors. He said CIRM’s existence is essential because it “funds [stem cell-based] research through the [financial] valley of death.” He further explained that CIRM is the only funding entity that takes basic stem cell research all the way through the clinical pipeline into a therapy.

Improving bone marrow transplants

judith shizuru

Judith Shizuru

Next, we heard a talk from Judith Shizuru on ways to improve current bone-marrow transplantation techniques. She explained how this form of stem cell transplant is “the most powerful form of cell therapy out there, for cancers or deficiencies in blood formation.” Inducing immune system tolerance, improving organ transplant outcomes in patients, and treating autoimmune diseases are all applications of bone marrow transplants. But this technique also carries with it toxic and potentially deadly side effects, including weakening of the immune system and graft vs host disease.

Shizuru talked about her team’s goal of improving the engraftment, or survival and integration, of bone marrow stem cells after transplantation. They are using an antibody against a molecule called CD117 which sits on the surface of blood stem cells and acts as an elimination signal. By blocking CD117 with an antibody, they improved the engraftment of bone marrow stem cells in mice and also removed the need for chemotherapy treatment, which is used to kill off bone marrow stem cells in the host. Shizuru is now testing her antibody therapy in a CIRM-funded clinical trial in humans and mentioned that this therapy has the potential to treat a wide variety of diseases such as sickle cell anemia, leukemias, and multiple sclerosis.

Tackling stroke and heart disease

img_1327We also heard from two CIRM-funded professors working on cell-based therapies for stroke and heart disease. Gary Steinberg’s team is using human neural progenitor cells, which develop into cells of the brain and spinal cord, to treat patients who’ve suffered from stroke. A stroke cuts off the blood supply to the brain, causing the death of brain cells and consequently the loss of function of different parts of the body.  He showed emotional videos of stroke patients whose function and speech dramatically improved following the stem cell transplant. One of these patients was Sonia Olea, a young woman in her 30’s who lost the ability to use most of her right side following her stroke. You can read about her inspiring recover post stem cell transplant in our Stories of Hope.

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Joe Wu followed with a talk on adult stem cell therapies for heart disease. His work, which is funded by a CIRM disease team grant, involves making heart cells called cardiomyocytes from human embryonic stem cells and transplanting these cells into patient with end stage heart failure to improve heart function. His team’s work has advanced to the point where Wu said they are planning to file for an investigational new drug (IND) application with the US Food and Drug Administration (FDA) in six months. This is the crucial next step before a treatment can be tested in clinical trials. Joe ended his talk by making an important statement about expectations on how long it will take before stem cell treatments are available to patients.

He said, “Time changes everything. It [stem cell research] takes time. There is a lot of promise for the future of stem cell therapy.”

How stem cells are helping change the face of medicine, one pioneering patient at a time

/ Kevin McCormack / 6 Comments

One of the many great pleasures of my job is that I get to meet so many amazing people. I get to know the researchers who are changing the face of medicine, but even more extraordinary are the people who are helping them do it, the patients.

Attacking Cancer

Karl

Karl Trede

It’s humbling to meet people like Karl Trede from San Jose, California. Karl is a quiet, witty, unassuming man who when the need arose didn’t hesitate to put himself forward as a medical pioneer.

Diagnosed with throat cancer in 2006, Karl underwent surgery to remove the tumor. Several years later, his doctors told him it had returned, only this time it had spread to his lungs. They told him there was no effective treatment. But there was something else.

“One day the doctor said we have a new trial we’re going to start, would you be interested? I said “sure”. I don’t believe I knew at the time that I was going to be the first one, but I thought I’d give it a whirl.”

Karl was Patient #1 in a clinical trial at Stanford University that was using a novel approach to attack cancer stem cells, which have the ability to evade standard anti-cancer treatments and cause the tumors to regrow. The team identified a protein, called CD47, that sits on the surface of cancer stem cells and helps them evade being gobbled up and destroyed by the patient’s own immune system. They dubbed CD47 the “don’t eat me” signal and created an antibody therapy they hoped would block the signal, leaving the cancer and the cancer stem cells open to attack by the immune system.

The team did pre-clinical testing of the therapy, using mice to see if it was safe. Everything looked hopeful. Even so, this was still the first time it was being tested in a human. Karl said that didn’t bother him.

“It was an experience for me, it was eye opening. I wasn’t real concerned about being the first in a trial never tested in people before. I said we know that there’s no effective treatment for this cancer, it’s not likely but it’s possible that this could be the one and if nothing else, if it doesn’t do anything for me hopefully it does something so they learn for others.”

It’s that kind of selflessness that is typical of so many people who volunteer for clinical trials, particularly Phase 1 trials, where a treatment is often being tried in people for the first time ever. In these trials, the goal is to make sure the approach is safe, so patients are given a relatively small dose of the therapy (cells or drugs) and told ahead of time it may not do any good. They’re also told that there could be some side effects, potentially serious, even life-threatening ones. Still, they don’t hesitate.

Improving vision

Rosie Barrero certainly didn’t hesitate when she got a chance to be part of a clinical trial testing the use of stem cells to help people with retinitis pigmentosa, a rare progressive disease that destroys a person’s vision and ultimately leaves them blind.

Rosalinda Barrero

Rosie Barrero

“I was extremely excited about the clinical trial. I didn’t have any fear or trepidation about it, I would have been happy being #1, and I was #6 and that was fine with me.”

 

Rosie had what are called retinal progenitor cells injected into her eye, part of a treatment developed by Dr. Henry Klassen at the University of California, Irvine. The hope was that those cells would help repair and perhaps even replace the light-sensing cells damaged by the disease.

Following the stem cell treatment, gradually Rosie noticed a difference. It was small things at first, like being able to make out the colors of cups in her kitchen cupboard, or how many trash cans were outside their house.

“I didn’t expect to see so much, I thought it would be minor, and it is minor on paper but it is hard to describe the improvement. It’s visible, it’s visible improvement.”

These are the moments that researchers like Henry Klassen live for, and have worked so tirelessly for. These are the moments that everyone at CIRM dreams of, when the work we have championed, supported and funded shows it is working, shows it is changing people’s lives.

One year ago this month our governing Board approved a new Strategic Plan, a detailed roadmap of where we want to go in the coming years. The plan laid out some pretty ambitious goals, such as funding 50 new clinical trials in the next 5 years, and at our Board meeting next week we’ll report on how well we are doing in terms of hitting those targets.

People like Karl and Rosie help motivate us to keep trying, to keep working as hard as we can, to achieve those goals. And if ever we have a tough day, we just have to remind ourselves of what Rosie said when she realized she could once again see her children.

“Seeing their faces. It’s pretty incredible. I always saw them with my heart so I just adore them, but now I can see them with my eye.”

Related Links:

Stem cell agency funds clinical trials in three life-threatening conditions

/ Kevin McCormack / 1 Comment

strategy-wide

A year ago the CIRM Board unanimously approved a new Strategic Plan for the stem cell agency. In the plan are some rather ambitious goals, including funding ten new clinical trials in 2016. For much of the last year that has looked very ambitious indeed. But today the Board took a big step towards reaching that goal, approving three clinical trials focused on some deadly or life-threatening conditions.

The first is Forty Seven Inc.’s work targeting colorectal cancer, using a monoclonal antibody that can strip away the cancer cells ability to evade  the immune system. The immune system can then attack the cancer. But just in case that’s not enough they’re going to hit the tumor from another side with an anti-cancer drug called cetuximab. It’s hoped this one-two punch combination will get rid of the cancer.

Finding something to help the estimated 49,000 people who die of colorectal cancer in the U.S. every year would be no small achievement. The CIRM Board thought this looked so promising they awarded Forty Seven Inc. $10.2 million to carry out a clinical trial to test if this approach is safe. We funded a similar approach by researchers at Stanford targeting solid tumors in the lung and that is showing encouraging results.

Our Board also awarded $7.35 million to a team at Cedars-Sinai in Los Angeles that is using stem cells to treat pulmonary hypertension, a form of high blood pressure in the lungs. This can have a devastating, life-changing impact on a person leaving them constantly short of breath, dizzy and feeling exhausted. Ultimately it can lead to heart failure.

The team at Cedars-Sinai will use cells called cardiospheres, derived from heart stem cells, to reduce inflammation in the arteries and reduce blood pressure. CIRM is funding another project by this team using a similar  approach to treat people who have suffered a heart attack. This work showed such promise in its Phase 1 trial it’s now in a larger Phase 2 clinical trial.

The largest award, worth $20 million, went to target one of the rarest diseases. A team from UCLA, led by Don Kohn, is focusing on Adenosine Deaminase Severe Combined Immune Deficiency (ADA-SCID), which is a rare form of a rare disease. Children born with this have no functioning immune system. It is often fatal in the first few years of life.

The UCLA team will take the patient’s own blood stem cells, genetically modify them to fix the mutation that is causing the problem, then return them to the patient to create a new healthy blood and immune system. The team have successfully used this approach in curing 23 SCID children in the last few years – we blogged about it here – and now they have FDA approval to move this modified approach into a Phase 2 clinical trial.

So why is CIRM putting money into projects that it has either already funded in earlier clinical trials or that have already shown to be effective? There are a number of reasons. First, our mission is to accelerate stem cell treatments to patients with unmet medical needs. Each of the diseases funded today represent an unmet medical need. Secondly, if something appears to be working for one problem why not try it on another similar one – provided the scientific rationale and evidence shows it is appropriate of course.

As Randy Mills, our President and CEO, said in a news release:

“Our Board’s support for these programs highlights how every member of the CIRM team shares that commitment to moving the most promising research out of the lab and into patients as quickly as we can. These are very different projects, but they all share the same goal, accelerating treatments to patients with unmet medical needs.”

We are trying to create a pipeline of projects that are all moving towards the same goal, clinical trials in people. Pipelines can be horizontal as well as vertical. So we don’t really care if the pipeline moves projects up or sideways as long as they succeed in moving treatments to patients. And I’m guessing that patients who get treatments that change their lives don’t particularly

Stem cell stories that caught our eye: fighting cancer, a cell’s neighborhood matters, funding next generation scientists

/ Don Gibbons / Leave a comment

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.

Reprogramming skin to fight cancer. Earlier CIRM-funded research showed that adult nerve stem cells can home to the residual brain cancer left behind after surgery and deliver a cancer killing agent directly to where it is most needed. Now a team at the University of North Carolina has shown it can use reprogramming techniques similar to the Nobel-prize winning iPS cell reprogramming method to turn a patient’s own skin cells directly into adult nerve stem cells. They then used those stem cells to deliver a cancer-fighting protein to mice with brain cancer and extended their lives.

“We wanted to find out if these induced neural stem cells would home in on cancer cells and whether they could be used to deliver a therapeutic agent. This is the first time this direct reprogramming technology has been used to treat cancer,” said the leader of the study, Shawn Hingtgen, in a UNC press release.

Cancer cells. (iStockPhoto)

Cancer cells. (iStockPhoto)

Many outlets picked up the release, including FoxNews, which overstated the lack of progress in the field.  Their piece suggests there had been no improvements “in more than 30 years,” which ignores several advances, but you can not argue with the quote they use from Hingtgen: “Patients desperately need a better standard of care.”

More evidence the neighborhood matters. Cells excrete substances that become the structure, known as the extracellular matrix (ECM), that holds them in place. Many regenerative medicine strategies count on using donor ECM to attract and hold stem cells, or use a synthetic material that mimics ECM. A team at the Institute for Research in Biomedicine in Barcelona has documented a strong feedback loop in which the ECM also directs which cells populate an area.

The work builds on a growing body of research we have written about that shows the neighborhood a stem cell finds itself in helps dictate what it will become. The study, published in eLife, focused on the tracheal tube in fruit flies.

“The biological context of these cells modifies not only their behavior but also their internal structure,” said the head of the project Jordi Casanova in a press release picked up by NewsMedical.net. “When we modify only the extracellular matrix, the cytoskeleton is also altered.”

The research team suggested that this form of intracellular communication has been preserved in evolution and has an important role in humans, including in inflammatory diseases and cancer.

Cancer therapy’s major step toward patients. We frequently point out that our mission is not to do research; it is to deliver therapies to patients. And that requires commercial partners that can do all the late stage work needed to bring a therapy to market. So, we are thrilled when the developers of a therapy we have fostered from the very earliest days in the lab announces they have complete the first half of a $75 million round of venture financing, and with major names from Silicon Valley, Lightspeed, Sutter Hill and Google Ventures.

The therapy, from the Stanford Lab of Irv Weissman, now being taken forward by the company he and colleagues founded, Forty Seven, has been shown to be effective against several types of cancer in animals and is now in an early phase human clinical trial funded by CIRM. We also funded the pre-clinical work for a total investment of more than $30 million in the therapy, which has promise to work synergistically with other therapies to wipe out notoriously difficult cancers. The company name comes from the therapy’s target on cancer stem cells, CD47.

Irv Weissman

Irv Weissman

“Targeting CD47 integrates the adaptive and innate immune systems, creating synergy with existing cancer-specific antibodies like rituximab, cetuximab and trastuzumab through ADCP, and potentially with T-cell checkpoint inhibitors through cross-presentation,” said Weissman in a company press release.

The online publication Xconomy wrote a longer piece providing more perspective on how the therapy could fit into the market and on CIRM’s role in its development.

The next generation in the lab.  The Guardsman, the student newspaper of City College, San Francisco, did a nice write up on our recent renewal of the colleges grant for one of our 17 current Bridges programs that train undergraduate and masters level students the ins-and-outs of working in a stem cell laboratory.

Rosa Canchari works with cell cultures in City College’s biotech laboratory. (Photo by Amanda Aceves/Special to The Guardsman)

Rosa Canchari works with cell cultures in City College’s biotech laboratory. (Photo by Amanda Aceves/Special to The Guardsman)

The current renewal has redirected the programs to have the students better understand the end user, the patient, and to get a firmer grasp on the regulatory and process development pathways needed to bring a new therapy to market. As program officer for this initiative, I will be meeting with all the program directors next week to discuss how best to implement these changes.

But, as the CCSF director Dr. Carin Zimmerman told the Guardsman, the program continues to generate highly valued skilled workers. Like many of our programs, CCSF offers its basic courses to students at the school beyond those enrolled in the CIRM internships, and even that more limited exposure to stem cell science often lands jobs.

“One of the reasons we have a hard time filling all these classes is because people take one or two classes and get hired,” said Carin Zimmerman.