Intraperitoneal immunotherapy of peritoneal carcinomatosis from solid tumors by trifunctional antibodies

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Abstract
2532 Background: Peritoneal carcinomatosis from solid tumors is a fatal diagnosis without standard treatment procedures, as concepts like peritonectomy and i.v./i.p. chemotherapy showed disappointing results. In this pilot study, we describe a new immunotherapeutic concept using trifunctional antibodies (trAb), which are able to redirect CTL to tumor cells and to induce active tumor immunity by activating Fcγ receptor type I and III positive accessory cells by their intact Fc region. Methods: In 9 patients with peritoneal carcinomatosis due to gastric cancer (6), ovarian cancer (2) and CUP (1) i.p. application of trAb was performed after surgery and/or ineffective chemotherapy. According to the antigen expression of autologous tumor cells, 2–5 doses of the trAb EpCAM x CD3 (5–80μg) or HER2/neu x CD3 (10–100 μg) were applicated by intraperitoneal infusion. After 4 weeks, patients received i.d./s.c. trAb + PBMC + irradiated tumor cells for restimulation. Immunological reactivity was tested by analyzing PBMC (1 week after boost) for specific tumor reactive CD4+/CD8+ T lymphocytes after restimulation with autologous tumor cells with the Miltenyi IFN Secretion Assay. Results: Antibody application was well tolerated without severe side effects. In 5/9 patients, tumor reactive CD4+/CD8+ T lymphocytes increased significantly indicating specific anti tumor immunity. Follow-up showed a mean survival of 11.8 months (median 8.0 months) after trAb therapy. 5/9 patients had a clinical response (stable disease, partial regression) with a mean time to progression of 4.6 months. Conclusions: In conclusion, immunotherapy using trAb may provide a new option for active treatment of peritoneal carcinomatosis, which is now evaluated in ongoing clinical trials.

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