Cited by 117Monoclonal and Polyclonal Antibodies ResearchIntraperitoneal and Appendiceal MalignanciesImmunotherapy and Immune Responses

Immunotherapy of malignant ascites with trifunctional antibodies

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Heiss, Markus M., Ströhlein, Michael A., Jäger, Michael, Kimmig, Rainer, Burges, Alexander, Schoberth, Alexandra, Jauch, Karl‐Walter, Schildberg, Friedrich‐Wilhelm +1 more·2005·International Journal of Cancer

Abstract

A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fcγ 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 μg. 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 μg. 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. © 2005 Wiley‐Liss, Inc.

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  • In an early clinical trial of patients with malignant ascites due to peritoneal carcinomatosis, administration of total doses of ertumaxomab as low as 40-140 μg led to complete elimination of tumor cells in ascites and disappearance of ascites accumulation in all patients.

    “In an early clinical trial of patients with malignant ascites due to peritoneal carcinomatosis, administration of total doses of ertumaxomab as low as 40-140 μg lead to a complete elimination of tumor cells in ascites, and disappearance of ascites accumulation in all patients. 29”
  • Ertumaxomab possesses the same hybrid Fc portion as catumaxomab and displays the same efficiency in vitro.

    “This triomab possesses the same hybrid Fc portion as catumaxomab, and displays the same efficiency in vitro. 29”

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Research works printed but not linked: 5

  1. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, et al. Peritoneal carcinomatosis from non-gynecologic malignan- cies: results of the EVOCAPE 1 multicentric prospective study. Can- cer 2000;88:358-63.
  2. Jackson GL, Blosser NM. Intracavitary chromic phosphate (32P) col- loidal suspension therapy. Cancer 1981;48:2596-8.
  3. Rambaldi A, Introna M, Colotta F, Landolfo S, Colombo N, Mangioni C, Mantovani A. Intraperitoneal administration of interferon beta in ovarian cancer patients. Cancer 1985;56:294-301.
  4. Stuart GC, Nation JG, Snider DD, Thunberg P. Intraperitoneal interferon in the management of malignant ascites. Cancer 1993;71:2027-30.
  5. Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood 2001;98:2526-34.

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Authors
Heiss, M. M., Ströhlein, M. A., Jäger, M., Kimmig, R., Burges, A., Schoberth, A., Jauch, K., Schildberg, F., & Lindhofer, H.
Affiliations
  • Witten/Herdecke University (DE)
  • Ludwig-Maximilians-Universität München (DE)
  • LMU Klinikum (DE)
Corresponding author
Heiss, Markus M.
Venue
International Journal of Cancer
Publisher
Wiley
Published
2005-09-14
Volume
117
Issue
3
Pages
435-443
ISSN
  • 0020-7136 (ISSN-L)
  • 1097-0215
OpenAlex
W1979885539
Cited by
117
References
37
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 5
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • International Journal of Cancer (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
trifunctional antibody, bispecific antibodies, malignant ascites, peritoneal carcinomatosis, intraperitoneal immunotherapy, EpCAM, HER2/neu, tumor cell killing, adverse events
MeSH terms
Ascites, Humans, Immunotherapy, Leukocyte Count, Middle Aged, Peritoneal Neoplasms, T-Lymphocytes, Tumor Necrosis Factor-alpha, Cytokines, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction

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