Outside-the-Box: The Rogosin Institute Is Fighting Cancer With Cancer Cells In Clinical Trials

Researchers at the Rogosin Institute are using cancer “macrobeads” to fight cancer.  Cancer cells in the beads secrete proteins which researchers believe could signal a patient’s cancer to stop growing, shrink or even die. The treatment is currently being tested in human clinical trials.

Two groundbreaking preclinical studies demonstrate for the first time that encapsulated mouse kidney cancer cells inhibit the growth of freely-growing cancer cells of the same or different type in a laboratory dish and in tumor-bearing animals. These findings support the hypothesis that cancer cells entrapped in seaweed-based gel, called “macrobeads,” send biological feedback or signals to freely-growing tumors outside the macrobead to slow or stop their growth. Both studies (cited below) are published in the on-line January 24, 2011 issue of Cancer Research, a publication of the American Association For Cancer Research.

Barry H. Smith, M.D., Ph.D., Director, The Rogosin Institute; Professor, Clinical Surgery, Weill Cornell Medical College

The Rogosin Institute, an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital and Weill Cornell Medical College, developed the cell encapsulation technology that facilitated production of the macrobead and applied this technology in conducting preclinical studies. The research team was headed by Barry H. Smith, M.D., Ph.D.,  the Director of The Rogosin Institute, Professor of Clinical Surgery at the Weill Cornell Medical College, and lead author of the studies. Findings in the studies to date are consistent with the hypothesis that when macrobeads are implanted in a host, the encapsulated cells are isolated from the host’s immune system but continue to maintain their functionality.

In addition to the standard preclinical in vivo and in vitro experiments, a clinical veterinary study was conducted in cats and dogs suffering from various spontaneous (non-induced) cancers. More than 40 animals were treated with the macrobead technology. Consistent results, measured both in terms of tumor response and animal well-being, occurred with prostate, liver and breast cancer, as well as lymphoma. Additional research revealed that regardless of the animal specie or type of cancer cell that was encapsulated, the macrobead technology inhibited cancer growth across all species and cancer types tested.  The results have included slowed tumor growth or, in some cases, necrosis and elimination of tumors and the restoration of a normal animal lifespan.

Cancer macrobead therapy has proceeded to human clinical testing. A Phase 1 trial in more than 30 patients evaluated the safety of macrobeads implanted in the abdominal cavity as a biological treatment of end-stage, treatment-resistant, epithelial-derived cancer. Based on the safety profile data, Phase 2 efficacy trials are in progress in patients with colorectal cancer, pancreatic cancer and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancers, including ovarian.  To date, the Rogosin Institute research team has not found evidence to indicate that placing mouse tumors in humans or other animal species causes harm or side-effects.

Scientists are testing whether macrobeads containing cancer cells can be implanted into patients and communicate with the patient’s tumor to stop growing, shrink or die.

Step 1:  Small beads are made from a seaweed-derived sugar called agarose and mixed with 150,000 mouse kidney cancer cells, and a second layer of agarose is added, encapsulating the cancer cells.

Step 2:  Within 3-to-10 days, 99% of the kidney cancer cells die.  The remaining cells have traits similar to cancer stem cells.

Step 3:  The stem cells begin to recolonize the bead.  The colonies increase in sufficient numbers within a few weeks to reach a stable state.

Step 4:  The beads begin to release proteins —  chemical signals reflecting that the beads have sufficient numbers of cells for growth regulators to kick in.

Step 5: Several hundred beads (depending on patient’s weight) are implanted in the abdominal cavity in a laparoscopic surgical procedure.  The cancer cells are trapped in the beads; preventing their circulation elsewhere in the body and protecting them from attack by the body’s immune system.

Step 6: In animal studies, researchers believe some proteins released from the beads reached tumors elsewhere in the body and tricked them into sensing that other tumor cells are nearby.

Step 7:  As a result, researchers believe tumors in some animals stopped growing, shrank or died.  The hypothesis is being tested in people with cancer.

Howard Parnes, M.D., Chief, Prostate & Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute

“This is a completely novel way of thinking about cancer biology,” says Howard L. Parnes, a researcher in the Division of  Cancer Prevention at the National Cancer Institute who is familiar with the work but was not involved with it. “We talk about thinking outside the box. It’s hard to think of a better example.” “They demonstrate a remarkable proof of principle that tumor cells from one animal can be manipulated to produce factors that can inhibit the growth of cancers in other animals,” Dr. Parnes says. “This suggests that these cancer inhibitory factors have been conserved over millions of years of evolution.”

“Macrobead therapy holds promise as a new option in cancer treatment because it makes use of normal biological mechanisms and avoids the toxicities associated with traditional chemotherapy,” said Dr. Barry Smith. “The results of our research show that this approach is not specific to tumor type or species so that, for example, mouse cells can be used to treat several different human tumors and human cells can be used to treat several different animal tumors.”

“Because cancer and other diseases are their own biological systems, we believe that the future of effective disease treatment must likewise be biological and system-based,” said Stuart Subotnick, CEO of Metromedia Bio-Science LLC. “Many of the existing therapies are narrow, targeted approaches that fail to treat diseases comprehensively. In contrast, our unique macrobead technology delivers an integrated cell system that alters disease processes and utilizes the body’s natural defense mechanisms. The goal is to repair the body and not merely treat the symptoms.”

It is well-known that proof of anti-tumor activity in treating animals does not represent guaranteed effectiveness in humans. But, assuming the macrobead therapy proves ultimately effective in humans, it would represent a novel approach to treating cancer and challenge existing scientific dogmas.

The cancer macrobead therapy described above is backed by Metromedia Company, a privately held telecommunications company which was run by billionaire John Kluge until his recent death. The Metromedia Biosciences unit has invested $50 million into the research.  If the treatment proves successful in humans, a large part of the revenue generated will be contributed to Mr. Kluge’s charitable foundation.

About Metromedia Bio-Science LLC

Metromedia Bio-Science LLC, in conjunction with The Rogosin Institute, utilizes the novel cell encapsulation technology to conduct research into the treatment of various diseases, including cancer and diabetes, and the evaluation of disease therapies. Metromedia Bio-Science LLC is an affiliate of Metromedia Company, a diversified partnership founded by the late John W. Kluge and Stuart Subotnick.

About The Rogosin Institute

The Rogosin Institute is an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital (NYPH) and Weill Cornell Medical College. It is one of the nation’s leading research and treatment centers for kidney disease, providing services from early stage disease to those requiring dialysis and transplantation. It also has programs in diabetes, hypertension and lipid disorders. The Institute’s cancer research program, featuring the macrobeads, began in 1995. The Rogosin Institute is unique in its combination of the best in clinical care with research into new and better ways to prevent and treat disease.

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Clinical Trials:

OU’s Non-Toxic Drug Makes Ovarian Cancer Cells Respond To New Treatment & Undergo Cell Suicide

“Cancer researchers at the University of Oklahoma Health Sciences Center have found a way to turn ineffective new cancer drugs into cancer-fighters. By using their patented chemical compound, SHetA2, researchers tricked cancer cells into responding to new treatments and undergoing cell suicide. … [T]he compound will work with several cancers, including lung, kidney, ovarian, colon and pancreatic cancer. … [The] research team … patented the SHetA2 Flex-Het and hope[s] to start clinical trials for the compound within a year. …

Cancer researchers at the University of Oklahoma Health Sciences Center have found a way to turn ineffective new cancer drugs into cancer-fighters. By using their patented chemical compound, SHetA2, researchers tricked cancer cells into responding to new treatments and undergoing cell suicide. The research appears in the journal Gynecologic Oncology.

Doris Mangiaracina Benbrook, Ph.D., is in her lab at the University of Oklahoma Health Sciences Center in Oklahoma City. (Photo: Univ. of Oklahoma Health Sciences Center)

“This discovery means that we can use our non-toxic cancer prevention pill to improve treatment for people who already have cancer,” said Doris Mangiaracina Benbrook, Ph.D., principal investigator on the project. “All studies to date have not found any side effects of taking our drug, giving hope that we can prevent cancer in healthy people, and improve treatment for cancer patients, without increasing toxicity.”

The latest study looked at an upcoming class of cancer treatment drugs that worked well in experimental models, but proved ineffective against many human tumors. Dr. Benbrook and her team decided to test their compound’s ability to “fix” the problem. It worked.

“The new chemotherapy drugs are antibodies that bind to cell surface receptors called ‘Death Receptors.’ The binding of the antibodies activates the death receptors in cancer cells and causes cell suicide with little harm to normal cells. Many cancers, however, are resistant to the antibodies,” Benbrook said. “We’ve shown that SHetA2 treatment can make ovarian and kidney cancer cells sensitive to the death receptor antibodies and kill the cancer.”

Benbrook said the compound will work with several cancers, including lung, kidney, ovarian, colon and pancreatic cancer.

“It would be a significant advancement in health care if we could avoid the severe toxicity and suffering that late stage cancer patients have to experience,” Benbrook said.

The synthetic compound, SHetA2, a Flex-Het drug, was created by Benbrook with the help of chemist Darrell Berlin at Oklahoma State University. The compound directly targets abnormalities in cancer cell components without damaging normal cells. The disruption causes cancer cells to die and keeps tumors from forming.

Flex-Hets or flexible heteroarotinoids are synthetic compounds that can change certain parts of a cell and affect its growth. Benbrook and her research team have patented the SHetA2 Flex-Het and hope to start clinical trials for the compound within a year. If the compound continues to be found safe, it would be developed into a pill to be taken daily like a multi-vitamin to prevent cancer. This new discovery means that the pill also could be used to make patients, who already have cancer, better respond to treatment.

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PhRMA Report Shows Record Number of Development Drugs to Treat Cancer; 63 Ovarian Cancer & 203 Solid Tumor Drugs Listed

“Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ : 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51 – 55)]. …”

“New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer

phrmalogoDenver, CO (April 1, 2009) – Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ Note: 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51-55)].

Nationwide, cancer is the second leading cause of death, affecting more than 10 million Americans, according to the National Cancer Institute. This year, more than half a million Americans are expected to die of cancer-more than 1,500 a day. In Colorado, the lifetime risk of cancer is 1 in 2 for males and 2 in 5 for females. The most commonly diagnosed cancer in the state is breast cancer, followed by prostate and lung cancer.

‘We released this report in Denver because of Colorado’s growing role in developing cancer medicines,’ said PhRMA Senior Vice President Ken Johnson, who unveiled the report at the State Capitol Building.

‘Oncology is one of Colorado’s core research competencies, so the President’s call to cure cancer resonates powerfully in our state,’ said Colorado Lt. Governor Barbara O’Brien. ‘We are proud that the cancer medicines now in the research pipeline in Colorado are contributing substantially to the incredible progress made in the last five years by biopharmaceutical companies in developing new and more effective cancer treatments. The nation must continue its strong commitment to the cutting-edge pharmaceutical research that will enable cancer patients to live longer, healthier, and more productive lives.’

billytauzin

Billy Tauzin, President and Chief Executive Officer, The Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA's mission is to conduct effective advocacy for public policies that encourage discovery of important new medicines for patients by pharmaceutical & biotechnology research companies.

‘I am one of those patients who was diagnosed with cancer and was given a new treatment that brought me from the brink of death back to life,’ says PhRMA President and CEO Billy Tauzin. ‘The men and women working for America’s pharmaceutical research companies are committed to developing new cancer medicines that, one day, could eradicate cancer all together.’

Cancer medicines being developed include 122 for lung cancer, the leading cause of cancer death in the United States; 107 for breast cancer, which is expected to strike more than 180,000 American women this year; 70 for colorectal cancer, which is the third most common cancer in both men and women; and 103 for prostate cancer, which this year is expected to kill 28,000 American men. Additional medicines target brain cancer, kidney cancer, ovarian cancer, pancreatic cancer, skin cancer, and others.

The medicines represent many cutting-edge approaches, including a drug that delivers a synthetic version of a substance derived from scorpions directly to brain tumor cells; a number of cancer vaccines; medicines that target and kill specific cancer cells; and treatments that activate the patient’s general immune system to destroy cancer.

‘Researchers are making exciting progress in the search for new cures and treatments for cancer. But these efforts are wasted if the medicines we develop aren’t accessible to patients who need them,’ said Johnson.

Help is available to patients in need through the Partnership for Prescription Assistance (PPA), a program sponsored by America’s pharmaceutical research companies. To date, the PPA has helped more than 5.7 million patients nationwide, including more than 72,000 people in Colorado. Since its launch in April 2005, the PPA bus tour has visited all 50 states and more than 2,500 cities to educate people about patient assistance programs.

The “Help is Here Express” is staffed by trained specialists able to quickly help uninsured and financially struggling patients access information on more than 475 patient assistance programs, including nearly 200 programs offered by pharmaceutical companies. When the “Help is Here Express” moves on, patients can visit PPA’s easy-to-use Web site (www.pparx.org) or call the toll-free phone number (1-888-4PPA-NOW).

Click here to read Medicines in Development for Cancer 2009. [Adobe Reader PDF Doc.]

Read the backgrounder fact sheet here.

______________________________________________________

Pharmaceutical Research & Manufacturers of America

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $50.3 billion in 2008 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.2 billion in 2008.

PhRMA Internet Address: www.phrma.org

For information on stories of hope and survival, visit: http://sharingmiracles.com/

PhRMA en Español: www.nuestraphrma.org

For information on how innovative medicines save lives, visit: www.innovation.org

For information on the Partnership for Prescription Assistance, visit: www.pparx.org

For information on the danger of imported drugs, visit: www.buysafedrugs.info”

SourceNew Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer, Press Release, Pharmaceutical Research and Manufacturers of America, April 1, 2009.

Massachusetts General Hospital Cancer Center To Genetically Profile All Patient Tumors

“The Massachusetts General Hospital Cancer Center has recently opened a new Translational Research Laboratory that will uncover the genetic codes and gene mutations from almost all of its cancer patients. … By embarking on such an ambitious approach, Cancer Center pathologists and oncologists hope to gather specific information about tumor properties that will lead to targeted therapies and better personalized treatments. Mass General will be the first and only cancer center to conduct molecular profiling of positive biopsies and tumors from all patients as part of basic patient care. …”

Genetic profiling

09/Mar/2009

massgenlab

Massachusetts General Hospital Cancer Center Opens Molecular Pathology Lab to Genetically Profile All Patient Tumors

The Massachusetts General Hospital Cancer Center has recently opened a new Translational Research Laboratory that will uncover the genetic codes and gene mutations from almost all of its cancer patients. Previously only a sampling of patients had their tumors analyzed in such a comprehensive fashion.

By embarking on such an ambitious approach, Cancer Center pathologists and oncologists hope to gather specific information about tumor properties that will lead to targeted therapies and better personalized treatments. Mass General will be the first and only cancer center to conduct molecular profiling of positive biopsies and tumors from all patients as part of basic patient care.

Scientists and researchers have already identified over 110 genetic mutations responsible for causing tumor growth, many of which are involved in several different types of cancers. Codirectors of the Transplational Research Laboratory, Leif Ellisen, MD, PhD, and A. John Iafrate, MD, PhD, have equipped the lab with state-of-the-art robotic technology, which will make it possible to quickly genotype tumor specimens within a short period of time.

‘This new and improved classification of cancers that we are doing is intended to give our oncologists more information about a individual patient’s cancer, so they can treat it in a very specific way, thereby significantly increasing the odds of success,’ says Iafrate.

Several new cancer drugs that are currently available or in development are able to block some of the mutations and pathways that cause tumor cells to proliferate. By targeting tumor gene mutations with these smart drugs, doctors may be able to eradicate malignant cells without using traditional treatments like chemotherapy and radiation, which have significant side effects.

The lab’s new tumor genotyping initiative should also expedite the time it takes to find the right drug for the right patient. According to Ellisen, ‘If we are able to identify a mutation in, say, a case of lung cancer, and we know that a particular drug has been successful in treating colon cancer patients with the same mutation, then we have good reason to believe that drug will work turning off the cancer-causing mutation in the lung cancer patient as well.’

The lab will start with the genotyping of Mass General’s lung cancer patients and phase in different disease groups over the next few weeks. It is anticipated that the profiling of all possible patient tumors will occur gradually over the coming months.

Learn more about research at the Cancer Center

Cited SourceMassachusetts General Hospital Cancer Center opens molecular pathology lab to genetically profile all patient tumors, News, Massachusetts General Hospital, Mar. 9, 2009.

Update:

  • Making Personalized Cancer Care Routine, In Depth, NCI Cancer Bulletin, Volume 6 / Number 11, National Cancer Institute, June 2, 2009 (noting that Massachusetts General Hospital & Memorial Sloan-Kettering Cancer Center are performing genetic profiling of all lung cancer tumors).