TRION Pharma: Trifunctional Antibody Catumaxomab Kills Cancer Stem Cells
Cancer stem cells (CSC) are defined as “tumor-initiating cells” that have the capacity to self-renew and to give rise to the variety of differentiated cells found in the malignancy. Chemotherapies have been shown to enrich CSC in the remaining tumors. CSC of solid tumors are characterized by different surface markers including EpCAM, the target antigen of catumaxomab.
Using patient samples from a pivotal phase II/III study, TRION detected the presence of cancer stem cells (CD133+/EpCAM+) in the peritoneal fluids of 62% of analyzed MA patients with different underlying primary tumor entities including ovarian, gastric and pancreatic cancer. Following catumaxomab treatment of four i.p. infusions (10µg day 0, 20µg day 3, 50µg day 7 and 150µg day 10), the CD133+/EpCAM+ cells were completely eliminated from the peritoneal fluids of all MA patients analyzed, irrespective of the underlying cancer. In the control group (paracentesis only) however, CD133+/EpCAM+ cells remained in the peritoneal fluids of all 6 patients analyzed.
“Destroying cancer stem cells means fighting cancer at its roots”, says Horst Lindhofer, CEO of TRION Pharma. “Catumaxomab’s efficacy against this particularly aggressive and resistant population of cancer cells further supports its therapeutic potential for the treatment of EpCAM-positive carcinomas.”
Catumaxomab (Removab®) is presently the only approved therapeutic antibody targeting EpCAM, a surface antigen that is widely expressed in the most frequent forms of human cancer. On April 20th this year, Removab® received EU approval for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinomas. Removab® is the first product world-wide to receive a regulatory approval for this indication. With its trifunctional mode of action, Removab® represents a new generation of antibodies using the body’s own immune system to help fight the tumor cells. Catumaxomab was invented by TRION Pharma and has been developed with Fresenius Biotech. Removab® is produced by TRION Pharma and marketed by Fresenius Biotech. Removab® has been launched in Germany and will subsequently be introduced in other European countries.
Malignant Ascites:
Malignant ascites can be caused by different carcinomas. Abdominal spread of cancer cells leads to an accumulation of fluid in the abdominal cavity and is associated with a poor prognosis. The most commonly used treatment of malignant ascites is puncture (paracentesis), which has to be carried out on average every one to two weeks and can lead to complications such as infection and fluid or protein deprivation. The trifunctional antibody Removab® is known to kill cancer cells in the peritoneal cavity and therefore attacks the primary cause of ascites formation.
EpCAM:
EpCAM or epithelial cell adhesion molecule is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas, such as breast, lung, colorectal, gastric, prostate and ovarian cancer. Catumaxomab (Removab®) is the only approved anti-EpCAM antibody available.
Triomab®: Trifunctional antibodies
Triomab® antibodies bind to cancer-specific surface antigens and recruit both T cells as well as accessory cells, such as macrophages, dendritic cells and natural killer cells, to the tumor site. As a result, they provide for a new quality of cancer cell killing, activating both arms of the immune system – the adaptive one with cytotoxic T cells as effectors and the innate one including accessory effector cells. Triomab® antibodies are therefore very effective in destroying cancer cells and show a therapeutic effect at very low doses. Triomab® antibodies are a development of TRION Pharma GmbH.
Catumaxomab (Removab®):
Catumaxomab (Removab®) is the most advanced Triomab® trifunctional antibody (anti-EpCAM x anti-CD3). It received EU market approval for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinomas in 2009. Catumaxomab is not only the first drug indicated for the treatment of malignant ascites, but also the first approved bispecific, trifunctional antibody worldwide. It is produced by TRION Pharma and marketed by TRION’s partner Fresenius Biotech.
TRION Pharma GmbH is a biopharmaceutical company developing trifunctional antibodies (Triomab®) in collaboration with Fresenius Biotech. The trifunctional antibodies are produced at TRION’s site in Munich, Germany, and are based on a proprietary platform technology for which TRION has secured IP rights around the world. For more information please visit the company's website at www.trionpharma.com.
TRION Research GmbH is a strategic partner of TRION Pharma focusing on the generation of novel Triomab® candidates and specialized clinical analytics.
Fresenius Biotech GmbH, a company of the Fresenius health care group, is focused on the development, marketing and commercialization of biopharmaceuticals in the fields of oncology and transplantation medicine. Fresenius Biotech is a German company with headquarters in Munich. For further information please visit www.fresenius-biotech.com. Removab® is a registered trade mark of Fresenius Biotech.
Fresenius SE is a German health care group with international operations, providing products and services for dialysis, hospital and outpatient medical care. In 2008, group sales were approx. € 12.3 billion. On March 31, 2009 the Fresenius Group had 126,849 employees worldwide. For more information please visit www.fresenius.com.