title: Immunotherapy of malignant ascites with trifunctional antibodies.
abstract: A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fcgamma receptor type I/III+ cells (macrophages, NK-cells and DC). These trifunctional antibodies (trAb) lead to efficient specific killing of targeted tumor cells without any pre- or co-stimulation. This concept was investigated in vivo in patients with malignant ascites in a clinical situation that allowed monitoring of tumor cell elimination and correlation with clinical effects. In a prospective study, 8 patients with malignant ascites due to peritoneal carcinomatosis were treated with intraperitoneal application of trAb, which bound either the EpCAM- or Her2/neu-antigen on tumor cells. Treatment consisted of 4-6 applications within 9-23 days with a total amount of 145-940 microg. Seven of eight patients required no further paracentesis during follow-up or until death with a mean paracentesis-free interval of 38 weeks (median = 21.5, range = 4-136). Tumor cell monitoring showed a complete elimination of tumor cells in ascites already at total doses as low as 40-140 microg. Clinical response with disappearance of ascites accumulation was seen in all patients, which was correlated with elimination of tumor cells (p = 0.0014). Severe adverse events were not observed. Clinically relevant side effects were fever, moderate abdominal pain and skin reactions. Intraperitoneal immunotherapy with trAb showed convincing efficacy in patients with malignant ascites. This treatment offers new therapeutic options for patients with peritoneal carcinomatosis.
authors.affiliation: Department of Surgery, Klinikum Grosshadern, Ludwig Maximilians University Munich, Germany. heissm@kliniken-koeln.de
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heiss
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ströhlein
authors.forename: Michael
authors.initials: M
authors.lastname: Jäger
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schoberth
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Schildberg
authors.forename: Horst
authors.initials: H
authors.lastname: Lindhofer
mesh_terms: D001201:Ascites / Q000097:blood / Q000276:immunology* / Q000628:therapy; D016207:Cytokines / Q000097:blood; D017931:DNA Primers; D006801:Humans; D007167:Immunotherapy; D007958:Leukocyte Count; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha