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Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer
Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057, Switzerland
Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307, Germany
Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307, Germany
* Author to whom correspondence should be addressed.
Received: 13 January 2012; in revised form: 14 February 2012 / Accepted: 16 February 2012 / Published: 22 February 2012
Abstract: Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.
Keywords: antibodies; dendritic cells; immunotherapy; prostate cancer; T cells
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Kiessling, A.; Wehner, R.; Füssel, S.; Bachmann, M.; Wirth, M.P.; Schmitz, M. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer. Cancers 2012, 4, 193-217.
Kiessling A, Wehner R, Füssel S, Bachmann M, Wirth MP, Schmitz M. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer. Cancers. 2012; 4(1):193-217.
Kiessling, Andrea; Wehner, Rebekka; Füssel, Susanne; Bachmann, Michael; Wirth, Manfred P.; Schmitz, Marc. 2012. "Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer." Cancers 4, no. 1: 193-217.