prostate cancer

The California Institute for Regenerative Medicine (CIRM) awards $5.8 million for prostate cancer research to USC 

/ Esteban Cortez / 1 Comment

The American Cancer Society estimates that this year in the United States, there will be 268,490 new cases of prostate cancer. It also estimates that 34,500 men will die from the cancer in 2022. Other than skin cancer, prostate cancer is the most common cancer in American men.  

These stark statistics are why the California Institute for Regenerative Medicine (CIRM) has awarded a $5.8 million grant to researchers at the University of Southern California to begin conducting preclinical studies using an innovative treatment for prostate cancer, known as synthetic immune receptor (SIR-T) therapy. 

“We have a homegrown USC technology which shows a lot of promise. If the path that we are on ultimately proves successful, it could revolutionize the treatment of not only prostate cancer but also other cancers,” said principal investigator Dr. Preet M. Chaudhary, a professor of medicine at the Keck School of Medicine of USC.  

A new approach to immunotherapy 

CAR-T cell therapy—which is now approved by the U.S. Food and Drug Administration (FDA) to treat several blood cancers—has been revolutionary for certain patients. In CAR-T therapy, a patient’s T-cells—a key part of their immune system—are extracted and genetically engineered to express the chimeric antigen receptor (CAR). The modified T-cells are then reinjected into the patient, where CAR enables them to selectively seek out, bind to, and kill cancer cells. 

But its success in treating blood cancers has not translated into effectiveness against solid tumor cancers, such as prostate, breast, brain, gastrointestinal, skin and lung cancer.  

“The bottom line is that people have tried to replicate the success of CAR-T cell therapy with solid tumor cancers, and have been mostly unsuccessful,” Chaudhary said. 

SIR-T therapy, in contrast, uses different receptors that more closely resemble the body’s natural T-cells. Chaudhary and his team tested thousands of prototypes over an eight-year period to develop receptors that are effective and safe for solid tumors, including prostate cancer. An initial round of tests in mice yielded very promising results, prompting Chaudhary to apply for funding from CIRM. 

What’s next? 

With CIRM funding, Chaudhary and his team can now begin conducting preclinical trials of SIR-T therapy. Their research over the next two and a half years will culminate in an application for FDA approval to begin clinical trials in humans.  

Chaudhary’s lab is also testing SIR-T therapy for other types of cancer, including melanoma, kidney cancer, lymphoma and a different molecule involved in prostate cancer. 

“This technology has a lot of different applications, so we are working to ensure the platform works across disease types,” Chaudhary said. “The series of grants we’ve received reflects a lot of excitement about the SIR-T platform.” 

To learn more about the work CIRM has funded to better understand solid tumors, visit our Solid Tumor Fact Sheet web page.  

Stem cell agency invests in therapy using killer cells to target colorectal, breast and ovarian cancers

/ Kevin McCormack / Leave a comment

While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.

BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.

This is the 78th clinical trial funded directly by the Stem Cell Agency.

BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”

They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.

“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.  

The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.

The awards went to:

ApplicationTitleInstitutionAward Amount
TRAN1-133442Optogenetic therapy for treating retinitis pigmentosa and
other inherited retinal diseases  		  Paul Bresge Ray Therapeutics Inc.  $3,999,553  
TRAN3-13332Living Synthetic Vascular Grafts with Renewable Endothelium    Aijun Wang UC Davis  $3,112,567    
TRAN1-13370Next generation affinity-tuned CAR for prostate cancer    Preet Chaudhary University of Southern California  $5,805,144  
TRAN1-3345Autologous MPO Knock-Out Hematopoietic Stem and
Progenitor Cells for Pulmonary Arterial Hypertension  		  Don Kohn UC Los Angeles  $5,207,434  

Creating a New Model for Diversity in Scientific and Medical Research

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Nature Cell Biology cover

The global pandemic has highlighted many of the inequities in our health care system, with the virus hitting communities of color the hardest. That has led to calls for greater diversity, equity and inclusion at every level of scientific research and, ultimately, of medical care. A recently released article in the journal Nature Cell Biology, calls for “new models for basic and disease research that reflect diverse ancestral backgrounds and sex and ensure that diverse populations are included among donors and research participants.”

The authors of the article are Dr. Maria T. Millan, CIRM’s President & CEO; Rick Horwitz Senior Advisor and Executive Director, Emeritus, Allen Institute for Cell Science; Dr. Ekemini Riley, President, Coalition for Aligning Science; and Dr. Ruwanthi N. Gunawardane, Executive Director of the Allen Institute for Cell Science.

Dr. Maria Millan, CIRM’s President & CEO, says we need to make these issues a part of everything we do. “At CIRM we have incorporated the principles of promoting diversity, equity and inclusion in our research funding programs, education programs and future programs. We believe this is essential to ensure that the therapies our support helps advance will reach all patients in need and in particular communities that are disproportionately affected and/or under-served.”

The article highlights how, in addition to cultural, environmental, and socioeconomic factors, genetic factors also appear to play a role in the way disease affects different people. For example, 50 percent of people in South Asia have genetic traits that increases their risk for severe COVID-19, in contrast only 16 percent of Europeans have those traits.

But while some studies have shown how African American men are at greater risk for prostate cancer than white men, most of the research in this and other areas has been done on white populations of European ancestry. Efforts are already underway to change these disparities. For example, the National Institutes of Health (NIH) has sponsored the All of Us Research Program, which is inviting one million people across the U.S. to help build one of the most diverse health databases in history.

The article in Nature Cell Biology stresses the need to account for diversity at the individual molecular, cellular and tissue level. The authors make the point that diversity in those taking part in clinical trials is essential, but equally essential is that diverse biology is accounted for in the scientific work that leads to the development of potential therapies in order to increase the likelihood of success.

That’s why the authors of the article say: “If we are to truly understand human biology, address health disparities, and personalize our treatments, we need to go beyond our important, ongoing efforts in addressing diversity and inclusion in the workforce and the delivery of healthcare. We need to improve the data we generate by including diverse populations among donors and research participants. This will require new models and tools for basic and disease research that more closely reflect the diversity of human tissues, across diverse donor backgrounds.”

“Greater diversity in biological studies is not only the right thing to do, it is crucial to helping researchers make new discoveries that benefit everyone,” said Ru Gunawardane, Executive Director of the Allen Institute for Cell Science.

To do this they propose creating “a suite” of research cells, such as human induced pluripotent stem cell (hiPSC) lines from a diverse group of individuals to reflect the racial, ethnic and gender composition of the population. Human iPSCs are cells taken from any tissue (usually skin or blood) from a child or adult that have been genetically modified to behave like an embryonic stem cell. As the name implies, these cells are pluripotent, which means that they can become any type of adult cell.

CIRM has already created one version of what this suite would look like, through its iPSC Repository, a collection of more than 2,600 hiPSCs from individuals of diverse ancestries, including African, Hispanic, Native American, East and South Asian, and European. The Allen Institute for Cell Science also has a collection that could serve as a model for this kind of repository. Its collection of over 50 hiPSC

lines have been thoroughly analyzed on both a genomic and biological level and could also be broken down to include diversity in donor ethnicity and sex.

Currently researchers use cells from different lines and often follow very different procedures in using them, making it hard to compare results from one study to another. Having a diverse and well defined collection of research cells and cell models that are created by standardized procedures, could make it easier to compare results from different studies and share knowledge within the scientific community. By incorporating diversity in the very early stages of scientific research, the scientists and therapy developers gain a more complete picture of the biology disease and potential treatments.  

Blocking pancreatic cancer stem cells

/ Kevin McCormack / 3 Comments
John Cashman

Cancer stem cells are one of the main reasons why cancers are able to survive surgery, chemotherapy and radiation. They are able to hide from those therapies and, at a future date, emerge and spread the cancer in the body once again.

Jionglia Cheng, PhD.

Jionglia Cheng, PhD., the lead author of a new CIRM-funded study, says that’s one of the reasons why pancreatic cancer has proved so difficult to treat.

“Pancreatic cancer remains a major health problem in the United States and soon will be the second most common cause of mortality due to cancer. A majority of pancreatic cancer patients are often resistant to clinical therapies. Thus, it remains a challenge to develop an efficacious clinically useful pancreatic cancer therapy.”

Dr. Cheng, a researcher with ChemRegen Inc., teamed up with John Cashman at the Human BioMolecular Research Institute and identified a compound, that seems to be effective in blocking the cancer stem cells.

In earlier studies the compound, called PAWI-2, demonstrated effectiveness in blocking breast, prostate and colon cancer. When tested in the laboratory PAWI-2 showed it was able to kill pancreatic cancer stem cells, and also was effective in targeting drug-resistant pancreatic cancer stem cells.

In addition, when PAWI-2 was used with a drug called erlotinib (brand name Tarceva) which is commonly prescribed for pancreatic cancer, the combination proved more effective against the cancer stem cells than erlotinib alone.

In a news release Dr. Cheng said: “In the future, this molecule could be used alone or with other chemotherapy albeit at lower doses, as a new therapeutic drug to combat pancreatic cancer. This may lead to much less toxicity to the patient,”

The study is published in the journal Scientific Reports.

Rave reviews for new Killer-T Cell study

/ Kevin McCormack / Leave a comment

Anytime you read a news headline that claims a new discovery “may treat all cancer” it’s time to put your skeptic’s hat on. After all, there have been so many over-hyped “discoveries” over the years that later flopped, that it would be natural to question the headline writer. And yet, this time, maybe, this one has some substance behind it.

Andrew Sewell with research fellow Garry Dolton. (Photo Credit: Cardiff University)

Researchers at the University of Cardiff in Wales have discovered a new kind of immune cell, a so-called “killer T-cell”, that appears to be able to target and kill many human cancer cells, such as those found in breast, prostate and lung cancer. At least in the lab.

The immune system is our body’s defense against all sorts of threats, from colds and flu to cancer. But many cancers are able to trick the immune system and evade detection as they spread throughout the body. The researchers found one T-cell receptor (TCR) that appears to be able to identify cancer cells and target them, but leave healthy tissues alone.

In an interview with the BBC, Prof. Andrew Sewell, the lead researcher on the study said: “There’s a chance here to treat every patient. Previously nobody believed this could be possible. It raises the prospect of a ‘one-size-fits-all’ cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population.”

The study, published in the journal Nature Immunology, suggests the TCR works by using a molecule called MR1 to identify cancerous cells. MR1 is found on every cell in our body but in cancerous cells it appears to give off a different signal, which enables the TCR to identify it as a threat.

When the researchers injected this TCR into mice that had cancer it was able to clear away many of the cells. The researchers admit there is still a long way to go before they know if this approach will work in people, but Sewell says they are encouraged by their early results.

“There are plenty of hurdles to overcome. However, if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time.”

CIRM is funding a number of clinical trials that use a similar approach to targeting cancers, taking the patient’s own immune T-cells and, in the lab, “re-educating” to be able to recognize the cancerous cells. Those cells are then returned to the patient where it’s hoped they’ll identify and destroy the cancer. You can read about those here , here, here, here, and here.

Predicting the Impact of Stem Cell Cures on Healthcare Burden in California

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A new independent report says developing stem cell treatments and cures for some of the most common and deadly diseases could produce multi-billion dollar benefits for California in reduced healthcare costs and improved quality and quantity of life.

The report, by researchers at the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics, looked at the value of hypothetical future interventions to reduce or cure cancer, diabetes, stroke and blindness.

Predicting the future is always complicated and uncertain and many groups are looking at the best models to determine the value and economic impact of cell and gene therapy as the first products are just entering the market. This study provides some insights into the potential financial benefits of developing effective stem cell treatments for some of the most intractable diseases affecting California today.

The impact could affect millions of people. In 2018 for Californians over the age of 50:

  • Nearly half were predicted to develop diabetes in their lifetime
  • More than one third will experience a stroke
  • Between 5 and 8 percent will develop either breast, colorectal, lung, or prostate cancer

The report says that a therapy that decreased the incidence of diabetes by 50 percent in Californians over the age of 51 would translate into a gain for the state of $322 billion in social value between now and 2050. Even just reducing diabetes 10% would lead to a gain of $60 billion in social value over the same period.

  • For stroke a 50 percent reduction would generate an estimated $229 billion in social value. A 10 percent reduction would generate $47 billion
  • For breast cancer a 50 percent reduction would generate $56 billion in social value; for colorectal cancer it would be $72 billion; for lung cancer $151 billion; and prostate cancer $53 billion. 

The impact of a cure for any one of those diseases would be enormous. For example, a 51-year-old woman cured of lung cancer could expect to gain a lifetime social value of almost half a million dollars ($467,275). That’s a measure of years of healthy life gained, of years spent enjoying time with family and friends and not wasting away or lying in a hospital bed.

The researchers say: “Though advances in scientific research defy easy predictions, investing in biomedical research is important if we want to reduce the burden of common and costly diseases for individuals, their families, and society. These findings show the value and impact breakthrough treatments could have for California.”

“Put in this context, the CIRM investment would be worthwhile if it increased our chances of success even modestly. Against the billions of dollars in disease burden facing California, the relatively small initial investment is already paying dividends as researchers work to bring new therapies to patients.”

The researchers determined the “social value” using a measure called a quality adjusted life-year (QALY). This is a way of estimating the cost effectiveness and consequences of treating or not treating a disease. For example, one QALY is equivalent to one year of perfect health for an individual. In this study the value of that year was estimated at $150,000. If someone is sick with, say, diabetes, their health would be estimated to be 0.5 QALY or $75,000. So, the better health a person enjoys and the longer they enjoy it the higher QALY score they accumulate. In the case of a disease affecting millions of people in that state or country that can obviously lead to very large QALY scores representing potentially billions of dollars.

Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

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Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

  

TITLE

  

INSTITUTION

 CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

  

U.C San Diego

  

$1,393,200

 
DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

  

U.C. Los Angeles

  

$1,404,000
DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

  

U.C. San Francisco

  

$900,000
DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

  

Salk Institute

  

$1,637,209
DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

  

City of Hope

  

$1,381,104
DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

  

Gladstone Institutes

  

$1,553,923
DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

  

U.C. San Diego

  

$865,282
DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

  

Stanford University

  

$865,282

 

 

Stem cell study holds out promise for kidney disease

/ Kevin McCormack / 6 Comments

Kidney failure

Image via youtube.com

Kidney failure is the Rodney Dangerfield of diseases, it really doesn’t get the respect it deserves. An estimated 660,000 Americans suffer from kidney failure and around 47,000 people die from it every year. That’s more than die from breast or prostate cancer. But now a new study has identified a promising stem cell candidate that could help in finding a way to help repair damaged kidneys.

Kidneys are the body’s waste disposal system, filtering our blood and cleaning out all the waste products. Our kidneys have a limited ability to help repair themselves but if someone suffers from chronic kidney disease then their kidneys are slowly overwhelmed and that leads to end stage renal disease. At that point the patient’s options are limited to dialysis or an organ transplant.

Survivors hold out hope

Italian researchers had identified some cells in the kidneys that showed a regenerative ability. These cells, which were characterized by the expression of a molecule called CD133, were able to survive injury and create different types of kidney cells.

Researchers at the University of Torino in Italy decided to take these findings further and explore precisely how CD133 worked and if they could take advantage of that and use it to help repair damaged kidneys.

In their findings, published in the journal Stem Cells Translational Medicine, the researchers began by working with a chemotherapy drug called cisplatin, which is used against a broad range of cancers but is also known to cause damage to kidneys in around one third of all patients. The team found that CD133 was an important factor in helping those damaged kidneys recover. They also found that CD133 prevents aging of kidney progenitor cells, the kind of cell needed to help create new cells to repair the kidneys in future.

Hope for further research

The finding opens up a number of possible lines of research, including exploring whether infusions of CD133 could help patients whose kidneys are no longer able to produce enough of the molecule to help repair damage.

In an interview in DD News, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine – praised the research:

“This is an interesting and novel finding. Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”

CIRM is funding several projects targeting kidney disease including four clinical trials for kidney failure. These are all late-stage kidney failure problems so if the CD133 research lives up to its promise it might be able to help people at an earlier stage of disease.

New developments in prostate cancer from UCLA

/ Karen Ring / Leave a comment

Today we’re bringing you a research update from a CIRM-funded team at UCLA that’s dedicated to finding a cure for prostate cancer. The team is led by Dr. Owen Witte, the director of the UCLA Broad Stem Cell Research Center and a Howard Hughes Investigator. Dr. Witte is well known for his work in leukemia and epithelial cancer stem cells. His interests have also expanded into prostate cancer and identifying new therapeutic targets for the most aggressive types of prostate tumors.

His team’s latest efforts, which were published in Cancer Cell last week, have unearthed a possible target for late-stage neuroendocrine prostate cancer treatment. This is a particularly nasty form of prostate cancer that is resistant to standard cancer treatments and is the cause of approximately a quarter of prostate cancer related deaths.

Myc-ing prostate cells cancerous

To study how neuroendocrine prostate cancer (NEPC) develops into uncontrollable tumors, Witte and his team developed a novel human stem cell model. They knew that patients with NEPC had abnormally high levels of a protein called N-Myc in their tumors. Witte had a hunch that maybe N-Myc was the “bad guy” that was transforming normal human prostate cells into deadly, aggressive cancer cells. So the team went on an adventure to find some answers.

Normal prostate cells (left) and neuroendocrine prostate cancer cells (right). (UCLA news release)

Normal prostate cells (left) and neuroendocrine prostate cancer cells (right). (UCLA news release)

They took normal human prostate cells from healthy donors and added the MYCN gene which then produced large amounts of N-Myc protein. After receiving an N-Myc boost, the normal basal cells developed into aggressive tumor cells. When these transformed cells were transplanted into mice, they generated NEPC tumors.

Naturally, Witte didn’t stop there. He was interested in understanding what was going on at the cellular level to transform normal prostate cells into cancer. Witte explained in a UCLA press release:

“Identifying the cellular changes that happen in cancer cells is key to the development of drugs that inhibit those changes and thereby stop the progression of the disease.”

 

Finding drugs that target prostate cancer

Further experiments revealed that N-Myc was required for maintaining the deadly nature of the NEPC tumors. If N-Myc expression was disrupted, then the tumors in the mice actually shrank. After establishing N-Myc as a therapeutic target, they went on a hunt for drugs that could block its tumor amplifying activity.

They tested a drug that originally was designed to treat childhood brain cancers that also had an N-Myc related cause. The drug, CD532, acts on a protein called Aurora A kinase. The kinase physically interacts with N-Myc and is required to keep N-Myc stable and able to do its job. When mice with NEPC tumors were treated with CD532, the effects were dramatic – their tumors shrank by as much as 80%.

Witte believes that some of the cellular mechanisms behind the growth of different cancers are conserved. He explained,

Owen Witte and first author John Lee (UCLA).

Owen Witte and first author John Lee (UCLA).

“Kinase activity is known to be implicated in many types of cancers, including chronic myelogenous leukemia, which is no longer fatal for many people due to the success of Gleevec. I believe we can accomplish this same result for people with neuroendocrine prostate cancer.”

According to Witte, the next chapter in this story will be to find other drugs that can treat NEPC possibly by targeting N-Myc. Testing CD532 in clinical trials is also an option. Thus far, the drug has only been tested in preclinical experiments and hasn’t progressed into clinical trials for safety and efficacy testing in humans.

Related links:

Using baking ingredient to create “nano” bombs and destroy cancer stem cells

/ Kevin McCormack / Leave a comment

Nixon_30-0316a

“I am not a cook”. Richard Nixon and the baking ingredient that could help win the “war on cancer”

In 1971 President Richard Nixon declared a “war on cancer” and signed the National Cancer Act into law. Forty years later we’re still waging that war, and cancer is still one of the leading causes of death. But now researchers in Ohio have unveiled a new weapon; a nanobomb that targets cancer stem cells.

In treating invasive cancers the standard weapons are chemotherapy and radiation, but cancer stem cells are somehow able to evade these and lie dormant. Eventually they emerge from hiding and multiply and spread throughout the body, leading to a recurrence of the cancer.

So researchers at The Ohio State University Comprehensive Cancer Center turned to nanoparticles to try and target them. Nanoparticles for those of who aren’t up on the latest trendy science topics (something I plead guilty to) are particles between 1 and 100 nanometers in size. Just to put it in context, that’s about one billionth of a meter. In other words, very small indeed.

In the past when scientists tried to use nanoparticles to carry anti-cancer therapies such as therapeutic RNA to the tumor, the cancer cells simply enfolded the RNA nanoparticles in a kind of compartment called an endosome, which rendered them useless.

In a news release, principal investigator Xiaoming He said their new approach helps the nanoparticles escape from the endosomes and attack the cancer:

“We believe we’ve overcome this challenge by developing nanoparticles that include ammonium bicarbonate, a small molecule that vaporizes when exposing the nanoparticles to near-infrared laser light, causing the nanoparticle and endosome to burst, releasing the therapeutic RNA.”

In the study, published in Advanced Materials,   He and his team put micro-RNA miR-34a inside the nanoparticles. This is a molecule known to lower the levels of a  protein that cancer stem cells need for survival. When the ammonium bicarbonate was hit with the near-infrared laser it caused the endosomes to burst and released the miR-34a, killing the cancer cell.

When they tested this approach in a mouse model of human prostate cancer it significantly reduced the size of the tumors.

Because near-infrared lasers penetrate to about half an inch this method could be used for tumors near the skin surface, and for deeper ones would only require a minimally invasive surgery to deliver the necessary dose of light.

Ammonium bicarbonate, the ingredient used to help the nanoparticles swell up, is used by the food industry for some baked goods such as cookies and crackers. It’s a little odd to think that something used in such tasty treats could also be potentially deadly – think about that next time you are browsing the cookie aisle at the supermarket.