NDLI: Novel humanized and highly efficient bispecific antibodies mediate killing of prostate stem cell antigen-expressing tumor cells by CD8+ and CD4+ T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Arndt, Claudia Michalk, Irene Bornhäuser, Martin Cartellieri, Marc Töpfer, Katrin Stamova, Slava Temme, Achim Bachmann, Michael Feldmann, Anja Ehninger, Gerhard Koristka, Stefanie Lindemann, Dirk Schmitz, Marc Krone, Franziska
Description	Country affiliation: Germany Author Affiliation: Feldmann A ( Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.)
Abstract	Prostate cancer is the most common noncutaneous malignancy in men. The prostate stem cell Ag (PSCA) is a promising target for immunotherapy of advanced disease. Based on a novel mAb directed to PSCA, we established and compared a series of murine and humanized anti-CD3-anti-PSCA single-chain bispecific Abs. Their capability to redirect T cells for killing of tumor cells was analyzed. During these studies, we identified a novel bispecific humanized Ab that efficiently retargets T cells to tumor cells in a strictly Ag-dependent manner and at femtomolar concentrations. T cell activation, cytokine release, and lysis of target cells depend on a cross-linkage of redirected T cells with tumor cells, whereas binding of the anti-CD3 domain alone does not lead to an activation or cytokine release. Interestingly, both CD8+ and CD4+ T cells are activated in parallel and can efficiently mediate the lysis of tumor cells. However, the onset of killing via CD4+ T cells is delayed. Furthermore, redirecting T cells via the novel humanized bispecific Abs results in a delay of tumor growth in xenografted nude mice.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Bispecific Physiology Antibodies, Monoclonal, Humanized Antigens, Neoplasm Biosynthesis Cd4-positive T-lymphocytes Immunology Cd8-positive T-lymphocytes Neoplasm Proteins Prostatic Neoplasms Stem Cells Tumor Stem Cell Assay Pathology Cell Death Epitopes, T-lymphocyte Gpi-linked Proteins Antagonists & Inhibitors Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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