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.
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.
“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.
- Smith BH, Gazda LS, Conn BL, et. al. Integrated Systems and Technologies: Three-Dimensional Culture of Mouse Renal Carcinoma Cells in Agarose Macrobeads Selects for a Subpopulation of Cells with Cancer Stem Cell or Cancer Progenitor Properties. Cancer Res; 71(3); 716–24, published online first January 24, 2011; doi:10.1158/0008-5472. CAN-10-2254.
- Smith BH, Gazda LS, Conn BL, et. al. Integrated Systems and Technologies: Hydrophilic Agarose Macrobead Cultures Select for Outgrowth of Carcinoma Cell Populations That Can Restrict Tumor Growth. Cancer Res; 71(3); 725–35, published online first January 24, 2011; doi:10.1158/0008-5472. CAN-10-2258.
- Preclinical Studies Show Encapsulated Cancer Cells Slow or Stop Growth of Freely-Growing Tumors In Animals, Press Release, Metromedia Bio-Science LLC, January 25, 2011.
- Novel Effort To Fight Cancer With Cancer Cells, by John Winslow, Business Section, Wall Street Journal Online, January 25, 2011.
- Use of Mouse Renal Adenocarcinoma Cell-containing Agarose-agarose Macrobeads in the Treatment of Patients With End-stage, Treatment-resistant Epithelial-derived Cancer [Phase I Study], Clinical Trial Summary (NCT00283075), ClinicalTrials.gov.
- An Open-Label Phase 2 Efficacy Trial of the Implantation of Mouse Renal Adenocarcinoma Cell-Containing Agarose-Agarose Macrobeads in the Treatment of Patients With Treatment-Resistant, Metastatic Pancreatic or Colorectal Adenocarcinoma, Clinical Trial Summary (NCT01053013), ClinicalTrials.gov.
- An Open-Label, Phase 2 Efficacy Trial of the Implantation of Mouse Renal Adenocarcinoma Cell-Containing Agarose- Agarose Macrobeads in the Treatment of Patients With Castration-Resistant Prostate Cancer Resistant to Docetaxel, Clinical Trial Summary (NCT01174368), ClinicalTrials.gov.