title: The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting.
abstract: BACKGROUND
  Patients with gastric cancer benefit from perioperative chemotherapy, however, treatment is toxic and many patients will relapse. The trifunctional antibody catumaxomab targets EpCAM on tumor cells, CD3 on T cells, and the Fcγ-receptor of antigen-presenting cells. While in Europe catumaxomab is approved for treating malignant ascites, it has not been investigated in the perioperative setting and its exact immunological mode of action is unclear.
  
  
  METHODS
  In our study, gastric cancer patients received neoadjuvant platinum-based chemotherapy, one intraoperative application of catumaxomab, and 4 postoperative doses of intraperitoneal catumaxomab. Immunomonitoring was performed in 6 patients before surgery, after completion of catumaxomab treatment, and one month later.
  
  
  RESULTS
  Intraperitoneal application of catumaxomab caused an increased expression of activation markers on the patients' T cells. This was accompanied by a transient decrease in numbers of CXCR3(+) effector T cells with a T-helper (Th)-1 phenotype in the peripheral blood. All patients evidenced pre-existing EpCAM-specific CD4(+) and/or CD8(+) T cells. While these cells transiently disappeared from the blood stream after intraperitoneal application of catumaxomab, we detected increased numbers of peripheral EpCAM-specific cells and a modified EpCAM-specific T-cell repertoire 4 weeks after completion of treatment. Finally, catumaxomab also amplified humoral immunity to tumor antigens other than EpCAM.
  
  
  CONCLUSIONS
  Our findings suggest that catumaxomab exerts its clinical effects by (1) activating peripheral T cells, (2) redistributing effector T cells from the blood into peripheral tissues, (3) expanding and shaping of the pre-existing EpCAM-specific T-cell repertoire, and (4) spreading of anti-tumor immunity to different tumor antigens.
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Djordje
authors: D
authors: Atanackovic
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Henrike
authors: H
authors: Reinhard
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Sabrina
authors: S
authors: Meyer
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Stefanie
authors: S
authors: Spöck
authors: Institute for Pathology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Tobias
authors: T
authors: Grob
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Tim
authors: T
authors: Luetkens
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Sara
authors: S
authors: Yousef
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Yanran
authors: Y
authors: Cao
authors: Department of Stem Cell Transplantation; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: York
authors: Y
authors: Hildebrandt
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Julia
authors: J
authors: Templin
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Katrin
authors: K
authors: Bartels
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Nesrine
authors: N
authors: Lajmi
authors: Division of Virology; Medical University IBK; Innsbruck, Austria.
authors: Heribert
authors: H
authors: Stoiber
authors: Department of Stem Cell Transplantation; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Nicolaus
authors: N
authors: Kröger
authors: Fresenius Biotech GmbH; Munich, Germany.
authors: Judith
authors: J
authors: Atz
authors: Fresenius Biotech GmbH; Munich, Germany.
authors: Diane
authors: D
authors: Seimetz
authors: Department of General, Visceral, and Thoracic Surgery; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Jakob R
authors: JR
authors: Izbicki
authors: Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology; University Medical Center Hamburg-Eppendorf; Hamburg, Germany.
authors: Carsten
authors: C
authors: Bokemeyer
mesh_terms: D018033:Antibodies, Bispecific / Q000008:administration & dosage*; D005060:Europe; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D007155:Immunologic Factors; C522419:catumaxomab
keywords: EpCAM; T cells; adjuvant immunotherapy; catumaxomab; gastric cancer; tumor immunology
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