Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
Trifunctional bispecific antibodies (trAbs) used in tumor immunotherapy have the unique ability to recruit T cells toward antigens on the tumor cell surface and, moreover, to activate accessory cells through their immunoglobulin Fc region interacting with activating Fcγ receptors. This scenario gives rise to additional costimulatory signals required for T cell-mediated tumor cell destruction and induction of an immunologic memory. Here we show in an in vitro system that most effective trAb-dependent T-cell activation and tumor cell elimination are achieved in the presence of dendritic cells (DCs). On the basis of these findings, we devise a novel approach of cancer immunotherapy that combines the specific advantages of trAbs with those of DC-based vaccination. Simultaneous delivery of trAbs and in vitro differentiated DCs resulted in a markedly improved tumor rejection in a murine melanoma model compared with monotherapy.
We are indebted to Albert Geishauser, Nadine Hömberg and Christine Zehetmeier for expert technical assistance. We thank Jürgen Hess, Raymund Buhmann and Reinhard Zeidler for critically reading the manuscript. P Ruf and H Lindhofer appreciate the financial support for the trifunctional antibody Surek fostered within the collaborative project 0315229A of the Biochance SME innovative program of the Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research).
- 3.Valone FH, et al. (2001) Dendritic cell-based treatment of cancer: closing in on a cellular therapy. Cancer J. 7 Suppl 2:S53–61.Google Scholar
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