Results from two different studies demonstrate that advanced trifunctional antibodies such as catumaxomab (Removab?, Trion Pharma/Fresenius Biotech) can activate the immune system in a way that can otherwise only be achieved through vaccination.
The data were obtained by two independent research teams using catumaxomab in malignant ascites and gastric cancer, respectively. The results were presented at the 47th annual meeting of the American Society of Clinical Oncology(ASCO).
Trifunctional antibodies antibodies bind to cancer-associated 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. These antibodies are therefore very effective in destroying cancer cells and show a therapeutic effect at very low doses.
Catumaxomab is the most advanced 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.
In about half of the analyzed malignant ascites patients and the majority of gastric cancer patients, a significant increase of antibodies against tumor antigens was observed following the intraperitoneal administration of catumaxomab. In both studies, the antibody response was not restricted to catumaxomab?s target antigen EpCAM, but also included further cancer antigens suggesting the induction of a comprehensive humoral immune response against the individual tumor. Three of four patients who received a second treatment cycle showed an even stronger immune effect, comparable to the booster reaction known from repeated vaccination. In the gastric cancer study, cellular immune response was also analyzed and confirmed. The population of EpCAM-specific peripheral T cells was found to be substantially expanded, four weeks following the treatment.
Triggering immune response mechanisms
These new results confirm the drug?s unique capacity to trigger several immune response mechanisms at the same time. Catumaxomab not only induces direct tumor cell destruction ? as was presented during last year?s ASCO ? but also a long-term vaccination effect against the individual tumor.
?This vaccination effect could provide a decisive advantage over current mono- or bispecific antibody approaches: Permanent treatment with catumaxomab will not be needed? , says Horst Lindhofer, CEO of Trion Pharma. ?If we are next able to align these data with clinical outcome, this offers a paradigm shift in antibody-based cancer therapy: From chronic treatment to short-term application with long-term effects. This would lead to significant benefits, not only for cancer patients, but also for public healthcare systems.”