This Article Full Text (PDF) All Versions of this Article: 1087057109341766v1 14/8/980    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Hirschhaeuser, F. Articles by Mueller-Klieser, W. PubMed PubMed Citation Articles by Hirschhaeuser, F. Articles by Mueller-Klieser, W. Social Bookmarking                         What's this?

Test System for Trifunctional Antibodies in 3D MCTS Culture

Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany

Tobias Leidig

Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany

Bjoern Rodday

Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany

Carsten Lindemann

Eufets AG, Preclinical Research and Development, Idar-Oberstein, Germany

Wolfgang Mueller-Klieser

Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany, mue-kli{at}uni-mainz.de

The aim of the present study was to assess the feasibility of a 3D tumor cell culture model, that is, multicellular tumor spheroids (MCTSs) as an adequate model for micrometastases and therefore as a pharmacological model for efficacy testing of trifunctional therapeutic antibodies. Unlike conventional monolayer cultures, spheroids allow researchers to study parameters, such as 3D cell shape, 3D cell arrangement and microenvironment, and penetration efficiency of defense cells that may largely influence the efficacy of antibody treatment in vivo. The authors established a long-term coculture of human MCTSs with peripheral blood mononuclear cells (PBMCs) to test the anticancer effect of the trifunctional, bispecific antibody catumaxomab (anti-EpCAM x anti-CD3) or similar therapeutic molecules. The test system is accessible to various analytical methods and thus allows for characterizing multiple parameters, which can help elucidate the mode of action of immunotherapeutic anticancer treatment. For example, the novel approach enables precise, reproducible volume growth analysis of MCTSs under immunotherapeutic treatments. For evaluation of changes within individual spheroids, cryosections can be stained (e.g., for proliferating or apoptotic cells as well as infiltrating PBMCs). Molecular PCR-based assays or flow cytometric analyses allow for discrimination between different cell types, particularly leukocyte subtypes. Furthermore, MCTSs can be disaggregated to form standard monolayers for cell viability or plating efficiency experiments. For these reasons, the MCTS model is a powerful tool to analyze drug efficacy with various endpoints under highly reproducible, standardized conditions. (Journal of Biomolecular Screening 2009:980-990)

Key Words: catumaxomab • spheroids • coculture • trifunctional antibody • immunological tumor therapy

This version was published on September 1, 2009

Journal of Biomolecular Screening, Vol. 14, No. 8, 980-990 (2009)
DOI: 10.1177/1087057109341766


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?