Results in Phase I Trial Targeting Cancer Stem Cells

At the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO), University of Colorado Cancer Center researchers reported results of a Phase I trial of OMP-54F28 (FZD8-Fc), an investigational drug candidate discovered by OncoMed Pharmaceuticals targeting cancer stem cells (CSCs). The drug was generally well tolerated, and several of the 26 patients with advanced solid tumors experienced stable disease for greater than six months. Three trials are now open for OMP-54F28 (FZD8-Fc) in combinations with standard therapy for pancreatic, ovarian and liver cancers, being offered at the CU Cancer Center and elsewhere.

"These are optimistic results for one of the first targeted therapies for cancer stem cells," says Antonio Jimeno, MD, PhD, investigator at the CU Cancer Center, director of the university's Cancer Stem Cell-Directed Clinical Trials Program, and principal investigator of the clinical trial at the CU Cancer Center site. "And it is great to work with such a science-focused sponsor, whose vision aligns with ours: bringing to the clinic cutting-edge drugs and ideas that are focused on targeting CSCs. In the context of the collaboration between the Gates Center for Stem Cell Biology and the CU Cancer Center this was the second clinical trial we offered to our patients with the specific intent to eliminate the CSCs in their tumors."

OMP-54F28 (FZD8-Fc) is an antagonist of the Wnt pathway, a key CSC signaling pathway that regulates the fate of these cells. The Wnt pathway is known to be inappropriately activated in many major tumor types, including colon, breast, liver, lung and pancreatic cancers, and is critical for the function of CSCs. Because of this extensive validation, in the Jimeno lab and elsewhere, the Wnt pathway has been a major focus of anti-cancer drug discovery efforts. OMP-54F28 (FZD8-Fc) and a sister compound also developed by OncoMed, vantictumab (OMP-18R5), are two of the first therapeutic agents targeting this key pathway to enter clinical testing. In multiple preclinical models, OMP-54F28 (FZD8-Fc) has shown its effectiveness in reducing CSC populations, leading to associated anti-tumor activity, either as a single agent or when combined with chemotherapy.

"The ongoing line of work with this drug is an excellent example of the bench getting even closer to the bedside -- our lab work with the drug in patient-derived xenograft models of disease makes possible the clinical trials taking place at the University of Colorado Hospital next door," Jimeno says.

The Phase I clinical trial of OMP-54F28 (FZD8-Fc) is an open-label dose escalation study in patients with advanced solid tumors for which there was no remaining standard curative therapy. Patients are assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and initial signals of efficacy. The trial is conducted at Pinnacle Oncology Hematology in Scottsdale, Arizona, the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, and the CU Cancer Center under the direction of Principal Investigators Dr. Michael S. Gordon, Dr. David Smith and Dr. Antonio Jimeno, respectively.

The most common adverse events, mild to moderate and manageable, included dysgeusia (altered taste), fatigue, muscle spasms, decreased appetite, alopecia and nausea. One related Grade 3 or greater adverse event of Grade 3 increased blood phosphorus was reported. One moderate sacral insufficiency fracture occurred in one patient at the highest tested dose of 20 mg/kg every three weeks after 6 cycles.

"The drug is now being developed in combination with standard of care in three Phase 1b clinical trials, with the CU Cancer Center being one of the active sites," Jimeno says. "In pancreatic, ovarian and liver cancers, we hope that by adding anti-cancer stem cell drugs to standard of care, we can control proliferating cells within the tumor that could otherwise help the tumor regenerate in the face of existing chemotherapies."

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The above story is based on materials provided by University of Colorado Cancer Center. Note: Materials may be edited for content and length.

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Results in Phase I Trial Targeting Cancer Stem Cells

Results in Phase I trial of OMP-54F28, a Wnt inhibitor targeting cancer stem cells

PUBLIC RELEASE DATE:

31-May-2014

Contact: Erika Matich erika.matich@ucdenver.edu 303-524-2780 University of Colorado Denver

At the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO), University of Colorado Cancer Center researchers reported results of a Phase I trial of OMP-54F28 (FZD8-Fc), an investigational drug candidate discovered by OncoMed Pharmaceuticals targeting cancer stem cells (CSCs). The drug was generally well tolerated, and several of the 26 patients with advanced solid tumors experienced stable disease for greater than six months. Three trials are now open for OMP-54F28 (FZD8-Fc) in combinations with standard therapy for pancreatic, ovarian and liver cancers, being offered at the CU Cancer Center and elsewhere.

"These are optimistic results for one of the first targeted therapies for cancer stem cells," says Antonio Jimeno, MD, PhD, investigator at the CU Cancer Center, director of the university's Cancer Stem Cell-Directed Clinical Trials Program, and principal investigator of the clinical trial at the CU Cancer Center site. "And it is great to work with such a science-focused sponsor, whose vision aligns with ours: bringing to the clinic cutting-edge drugs and ideas that are focused on targeting CSCs. In the context of the collaboration between the Gates Center for Stem Cell Biology and the CU Cancer Center this was the second clinical trial we offered to our patients with the specific intent to eliminate the CSCs in their tumors."

OMP-54F28 (FZD8-Fc) is an antagonist of the Wnt pathway, a key CSC signaling pathway that regulates the fate of these cells. The Wnt pathway is known to be inappropriately activated in many major tumor types, including colon, breast, liver, lung and pancreatic cancers, and is critical for the function of CSCs. Because of this extensive validation, in the Jimeno lab and elsewhere, the Wnt pathway has been a major focus of anti-cancer drug discovery efforts. OMP-54F28 (FZD8-Fc) and a sister compound also developed by OncoMed, vantictumab (OMP-18R5), are two of the first therapeutic agents targeting this key pathway to enter clinical testing. In multiple preclinical models, OMP-54F28 (FZD8-Fc) has shown its effectiveness in reducing CSC populations, leading to associated anti-tumor activity, either as a single agent or when combined with chemotherapy.

"The ongoing line of work with this drug is an excellent example of the bench getting even closer to the bedside our lab work with the drug in patient-derived xenograft models of disease makes possible the clinical trials taking place at the University of Colorado Hospital next door," Jimeno says.

The Phase I clinical trial of OMP-54F28 (FZD8-Fc) is an open-label dose escalation study in patients with advanced solid tumors for which there was no remaining standard curative therapy. Patients are assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and initial signals of efficacy. The trial is conducted at Pinnacle Oncology Hematology in Scottsdale, Arizona, the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, and the CU Cancer Center under the direction of Principal Investigators Dr. Michael S. Gordon, Dr. David Smith and Dr. Antonio Jimeno, respectively.

The most common adverse events, mild to moderate and manageable, included dysgeusia (altered taste), fatigue, muscle spasms, decreased appetite, alopecia and nausea. One related Grade 3 or greater adverse event of Grade 3 increased blood phosphorus was reported. One moderate sacral insufficiency fracture occurred in one patient at the highest tested dose of 20 mg/kg every three weeks after 6 cycles.

"The drug is now being developed in combination with standard of care in three Phase 1b clinical trials, with the CU Cancer Center being one of the active sites," Jimeno says. "In pancreatic, ovarian and liver cancers, we hope that by adding anti-cancer stem cell drugs to standard of care, we can control proliferating cells within the tumor that could otherwise help the tumor regenerate in the face of existing chemotherapies."

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Results in Phase I trial of OMP-54F28, a Wnt inhibitor targeting cancer stem cells

Study identifies cell-cycle phase that primes stem cells …

by Krista Conger

Resting, adult stem cells of many types of tissues enter a reversible "alert" phase in response to a distant injury, according to a study in mice by researchers at the Stanford University School of Medicine.

The study describes for the first time a new phase in the resting portion of the cell cycle. It also explains how stem cells prime themselves to rapidly respond to tissue damage without prematurely committing to energetically expensive (and possibly unnecessary) cell division. These alert cells are distinct from fully resting or fully activated stem cells, and they divide and repair subsequent tissue damage much more quickly than do fully resting stem cells.

The findings imply that nearly any type of injury may put stem cells throughout the body on notice for possible future regenerative needs.

"These alert stem cells changed markedly in response to a distant muscle injury," said Thomas Rando, MD, PhD, professor of neurobiology and neurological sciences. "They are partially awake and are poised to respond to additional challenges and make new tissue as needed. This is a systemic, or whole-body, response to injury that has never been seen before."

The researchers suggest the alert phase represents a novel form of cellular memory similar to that displayed by the immune system, which relies upon prior experiences to drive future responses.

Rando, who also directs Stanford's Glenn Laboratories for the Biology of Aging, is the senior author of the study, published online May 25 in Nature. Postdoctoral scholar Joseph Rodgers, PhD, is the lead author.

Resting state?

The researchers were studying the response of mouse muscle stem cells, or satellite cells, to muscle injury. Conventional wisdom holds that adult stem cells are by nature quiescenta term that indicates a profound resting state characterized by small size and no cell division. It's a kind of cellular deep freeze. In contrast, most other cells cycle through rounds of DNA replication and cell division in discrete, well-defined phases. A quiescent stem cell can "wake up" and enter the cell cycle in response to local signals of damage or other regeneration needs.

Rando and his colleagues were studying this activation process in laboratory mice by watching how muscle stem cells in one leg respond to a nearby muscle injury in the same leg. (Mice were anesthetized prior to a local injection of muscle-damaging toxin; they were given pain relief and antibiotics during the recovery period.) The researchers had planned to observe the quiescent muscle stem cells in the uninjured leg as a control for their experiment. However, they instead saw something unexpected.

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Forget the dentist's drill, use lasers to heal teeth

Open wide, this won't hurt a bit. That might actually be true if the dentist's drill is replaced by a promising low-powered laser that can prompt stem cells to make damaged hard tissue in teeth grow back. Such minimally invasive treatment could one day offer an easy way to repair or regrow our pearly whites.

When a tooth is chipped or damaged, dentists replace it with ceramic or some other inert material, but these deteriorate over time.

To find something better, researchers have begun to look to regenerative medicine and in particular to stem cells to promote tissue repair. Most potential stem cell therapies require the addition of growth factors or chemicals to coax dormant stem cells to differentiate into the required cell type. These chemicals would be applied either directly to the recipient's body, or to stem cells that have been removed from the body and cultured in a dish for implantation.

But such treatments have yet to make it into the doctor's clinic because the approach needs to be precisely controlled so that the stem cells don't differentiate uncontrollably.

Praveen Arany at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, and his colleagues wondered whether they could use stem cells to heal teeth, but bypass the addition of chemicals by harnessing the body's existing mechanisms.

"Everything we need is in the existing tooth structure the adult stem cells, the growth factors, and exactly the right conditions," says Arany.

So they tried laser light, because it can promote regeneration in heart, skin, lung, and nerve tissues.

To mimic an injury, Arany's team used a drill to remove a piece of dentin the hard, calcified tissue beneath a tooth's enamel that doesn't normally regrow from the tooth of a rat. They then shone a non-ionising, low-power laser on the exposed tooth structure and the soft tissue underneath it. This allowed the light to reach the dental stem cells deep inside the pulp of the tooth.

Twelve weeks after a single 5-minute treatment, new dentin had formed in the cavity. Similar dentin production was seen in mice and in cultured human dental stem cells.

It not quite the end of the dentist's intervention though, they would still need to cap the tooth to protect it, because the stem cells that produce enamel are not present in adults.

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Forget the dentist's drill, use lasers to heal teeth

Veterinarian clinic offers alternative

By Heidi McKinley, correspondent

Until recently, the only treatment options for animals with degenerative tissue disease were pain relievers and anti-inflammatories.

Eastern Iowa Veterinary Specialty Center, however, soon will offer a promising new alternative.

The typical drug therapy doesnt solve the problem, said veterinarian Bob Harman, CEO of the company Vet Stem. It just reduces the inflammation.

Harmans company has partnered with EIVSC, which is in Cedar Rapids, to use an animals own cells for healing. This therapy is presented to owners as a way to regenerate tissue more naturally.

Were not using foreign (cells). Were not killing babies. Were not using embryos. Were not doing any of the stuff you see on 60 Minutes and CNN, Harman said. Were going to use the dogs own natural cells.

The process involves harvesting a sample from a pets fatty tissue, concentrating the cells in a lab and then injecting them back into the joint. The average dog will go 18 months to two years between therapies.

Stem cell therapy is most commonly used to treat arthritis; however, future applications could be used for possibly fatal diseases such as kidney failure, immune system malfunction (for example, dry eye) and traumatic injury.

The clinics motivation to offer the service came from the case of a 12-year-old sheltie/collie mix named Yurtie.

Yurtie is the first and only patient to receive stem cell therapy at the clinic. Jan Erceg adopted her after her previous owner, Kevin McClain, died from lung cancer in 2011. McClain had been living out of his car when Erceg, a paramedic, was dispatched to take him to the hospital. One of the dying mans last requests was for his dog to be taken care of, and Erceg has honored that request.

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Herpes-loaded stem cells used to kill brain tumors

Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs) -- a type of stem cell that gives rise to bone marrow tissue -- which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

"So, how do you translate this into the clinic?" asked Shah, who also is an Associate Professor at Harvard Medical School.

"We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking," he continued. "So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors."

Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. "Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers' solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma -- this time created from brain tumor cells that were resistant to the herpes virus -- the therapy led to increased animal survival.

"Our approach can overcome problems associated with current clinical procedures," Shah said. "The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors."

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Herpes-loaded stem cells used to kill brain tumors

Researchers: Dose of measles puts womans cancer into remission

A woman with an incurable cancer is now in remission, thanks, doctors say, to a highly concentrated dose of the measles virus.

For 10 years, Stacy Erholtz, 49, battledmultiple myeloma, a deadly cancer of the blood.

Doctors at the Mayo Clinic say she had received every type of chemotherapy drug available for her cancer and had undergone two stem cell transplants, only to relapse time and again.

Then researchers gave her and five other multiple myeloma patients a dose of a highly concentrated, lab-engineered measles virus similar to the measles vaccine.

In fact, the dose Erholtz received contained enough of the virus to vaccinate approximately 100 million people.

The idea here is that a virus can be trained to specifically damage a cancer and to leave other tissues in the body unharmed, said the lead study author, Dr. Stephen Russell.

Its a concept known as virotherapy and its been done before.

Mayo Clinic scientists say thousands of cancer patients have been treated with viruses but this is the first case of a patient with a cancer that had spread throughout the body going into remission.

Erholtz was cancer-free for nine months.

I think we succeeded because we pushed the dose higher than others have pushed it, Russell said. And I think that is critical. The amount of virus thats in the bloodstream really is the driver of how much gets into the tumors.

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Researchers: Dose of measles puts womans cancer into remission

Lung Institute Becomes Major Provider in Tampa Bay

Tampa, Florida (PRWEB) May 15, 2014

On Tuesday, May 20, Lung Institute is celebrating the first anniversary of its Tampa location. As a leader in regenerative medicine, Lung Institute has provided over 250 treatments to lung disease patients who previously had no hope for better breathing and regaining quality of life. Lung Institute treats lung diseases including pulmonary fibrosis and chronic obstructive pulmonary disease (COPD), a progressive disease that causes difficulty breathing, and is the third leading cause of death in the United States.

Led by Dr. Burton Feinerman, a world-renowned physician in the field of regenerative medicine, Lung Institute has performed hundreds of minimally invasive, outpatient stem cell treatments on patients with a variety of debilitating lung diseases. Stem cells are taken from the patients own blood or fat tissue. The treatments cue healing processes in the lungs, allowing patients to get back to normal, everyday activities and breathe easier.

Patients from around the United States, and the world, have traveled to Tampa to receive treatment. Since inception, Lung Institute has more than doubled its staff, and is poised for growth going into its second year. An anniversary celebration is being held on Tuesday, May 20, with a grand-prize giveaway of a free venous stem cell treatment* for one winner.

We provide hope to our patients, and an improved quality of life, said Dr. Feinerman. Now for our first anniversary, we have the opportunity to change another persons life, by giving away a free venous treatment.

Join us for Lung Institutes first anniversary celebration: When: Tuesday, May 20, 4 p.m. 7 p.m. Where: Lung Institute, 201 E. Kennedy Blvd., Suite 425, Tampa, FL 33602 What: Lung Institutes first anniversary celebration, with refreshments and giveaways including the grand-prize giveaway of a free venous stem cell treatment*! RSVP: Please call 855-469-5864 to RSVP or to learn more.

About Lung Institute At Lung Institute (LI), we are changing the lives of hundreds of people across the nation through the innovative technology of regenerative medicine. We are committed to providing patients a more effective way to address pulmonary conditions and improve quality of life. Our physicians, through their designated practices, have gained worldwide recognition for the successful application of revolutionary minimally invasive stem cell therapies. With over a century of combined medical experience, our doctors have established a patient experience designed with the highest concern for patient safety and quality of care. For more information, visit our website at LungInstitute.com, like us on Facebook or call us today at 1-855-469-5864.

*One grand prize: Venous stem cell procedure for one winner. Winner must be deemed medically eligible, as determined solely by Lung Institute and a Lung Institute physician, in order to receive treatment. If winner is not determined medically eligible, the prize will go to another entrant. Must be present at event to win. No purchase necessary.

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Top Northern Colorado Pain Management Doctors at Colorado Clinic Now Offering Stem Cell Procedures for Degenerative …

Boulder, Colorado (PRWEB) May 13, 2014

Colorado Clinic, the top pain management clinics in Greeley, Boulder and Loveland, is now offering nonoperative stem cell procedures to help relieve degenerative arthritis pain and avoid the need for joint replacement surgery. The procedures are offered by a Double Board Certified Colorado pain management doctor, with multiple options for the procedures. For more information and scheduling, call (303) 444-4141.

Currently in America there are over 1 million joint replacement procedures performed annually. This includes joint replacement for the shoulder, hip, knee and ankle. While these procedures typically work very well, they are truly meant as a last resort option since there are several risks involved with the operation. One of the main risks is that the implants used in joint replacement are not meant to last forever and revision surgeries are much more complicated than the initial. Therefore, joint replacement should be avoided for as long as possible.

Stem cell procedures are cutting-edge and now mainstream for helping repair arthritic damage in joints and providing pain relief from arthritis. Dr. Brad Sisson is a highly qualified pain management doctor at Colorado Clinic, and performs the outpatient stem cell procedures with either amniotic derived or bone marrow derived stem cells.

The amniotic fluid is obtained from consenting donors after a scheduled C-section, and has been shown to have a very high concentration of stem cells. The fluid is processed at an FDA regulated lab and contains no embryonic stem cells or fetal material. This alleviates any ethical concerns.

The bone marrow derived stem cells are harvested from the patient, and then are immediately processed to concentrate the stem cells, growth factors and platelets to inject into the area being treated.

To date, small published studies have shown excellent benefits for degenerative arthritis with stem cell procedures. Dr. Sisson performs the regenerative medicine treatments as an outpatient, and there is minimal risk involved with either of the procedures.

Colorado Clinic has several pain management centers in Northern Colorado including Boulder, Greeley and Loveland. Patients are currently being accepted at all of the locations for the stem cell procedures. For more information and scheduling with pain management Boulder trusts, call (303) 444-4141.

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Tagaytay mayor orders closure of stem cell clinic – Video

Tagaytay mayor orders closure of stem cell clinic
Professional Regulation Commission (PRC) confirms that alternative medicine Dr. Antonia Park does not appear in the database of Physician. Subscribe to the ABS-CBN News channel! - http://goo.gl/7l...

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