Major finding: Catumaxomab-induced T-cell activation eliminates tumor cells in malignant ascites.
Approach: Immunologic analysis was performed on peritoneal fluid after catumaxomab treatment.
Impact: Catumaxomab triggers an effective immune response in an immunosuppressed environment.
Malignant ascites (MA) is an abnormal collection of peritoneal fluid that arises when abdominal tumors spread and disrupt the regulation of fluid flow within the peritoneal cavity. In 2009, the European Medicines Agency approved intraperitoneal administration of the trifunctional antibody catumaxomab for the treatment of MA. Although the therapeutic benefit of catumaxomab has been well established, exactly how the antibody limits tumor burden and slows re-accumulation of ascites fluid within the immunosuppressed environment of MA remains unknown. To investigate potential molecular and immunologic mechanisms, Jäger and colleagues analyzed peritoneal fluid samples from MA patients receiving catumaxomab versus paracentesis in a phase II/III randomized clinical trial. Catumaxomab contains one antigen-binding site for the epithelial cell-adhesion molecule EpCAM and a second for the T-cell co-receptor CD3, in addition to a functional Fc domain. Because the majority of ascites-causing tumors express EpCAM, catumaxomab is a targeted immunotherapy that physically brings together tumor cells, T cells, and antigen-presenting cells. The authors found that catumaxomab treatment activated CD4+ and CD8+ T cells and reduced tumor burden in MA patients. Interestingly, catumaxomab also eliminated putative CD133+/EpCAM+ cancer stem cells from ascites fluid. Additional studies confirmed direct tumor cell killing and noted the release of proinflammatory cytokines in vitro. Together, the current findings support and offer mechanistic insight into the clinical benefit derived from catumaxomab treatment. The observation that catumaxomab activates a robust and specific immune response within the relatively immunosuppressed environment of MA should inform future development of novel targeted immunotherapies.
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