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- W2038049371 abstract "According to current views, in order for cancer immunotherapy to be successful it must target cancer stem cells (CSC) and counteract the multiple mechanisms involved in immune escape. Guided by these concepts, we have developed a combinatorial adoptive immunotherapeutic strategy which utilizes a monoclonal antibody (mAb) and cytotoxic T lymphocytes (CTL) in combination with continuous administration of low dose cyclophosphamide (metronomic chemotherapy) to target CSC and differentiated tumor cells, as well as activated pericytes in the tumor microenvironment. The targets selected are aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and chondroitin sulfate proteoglycan 4 (CSPG4). We now report that ALDH bright cells in squamous cell carcinoma of the head and neck (SCCHN) cell lines, which express high levels of ALDH1A1, are tumorigenic at low inoculum in immunodeficient mice, and particularly sensitive to recognition by ALDH1A1-specific T cells. The ALDH bright cells express CSPG4, a cell surface antigen functional in adhesion and migration. CSPG4 is also expressed on tumor associated activated pericytes which stabilize tumor blood vessels and provide vascular endothelial cells with survival signals. Administration of CSPG4-specific mAb and metronomic chemotherapy combined with intralesional adoptive transfer of ALDH1A1 peptide-specific CTL to mice bearing human SCCHN PCI-13-derived xenografts significantly reduced tumor growth and number of tumor cells with CSC phenotype. The antitumor effects of the immunotherapy we have developed were significantly higher than those of its individual components. These results argue in favor of the possibility that this combinatorial strategy may enhance the clinical efficacy of adoptive immunotherapy in SCCHN patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5605." @default.
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- W2038049371 date "2010-04-15" @default.
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- W2038049371 title "Abstract 5605: Targeting cancer stem cells in squamous cell carcinoma of the head and neck with combinatorial adoptive immunotherapy" @default.
- W2038049371 doi "https://doi.org/10.1158/1538-7445.am10-5605" @default.
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