体内・細胞内動態制御機能を搭載した熱ショックタンパク質の開発とワクチンデリバリーへの応用(誌上シンポジウム)

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Antigen delivery to antigen-presenting cells (APCs) is a key issue in developing effective cancer vaccines. Controlling the tissue distribution of antigens, which are administered in a peptide/protein or DNA form, can increase antigen-specific immune responses, including the induction of cytotoxic T lymphocytes. Heat-shock protein 70 (Hsp70), a member of a highly conserved family of molecular chaperones, forms complexes with a variety of tumor-related antigens via its polypeptide binding domain. Because Hsp70 is taken up by APCs through the recognition by Hsp receptors, such as CD91 and LOX-1, its application to antigen delivery systems has been examined both in experimental and clinical settings. A tissue distribution study revealed that Hsp70 is mainly taken up by the liver, especially by hepatocytes, after intravenous injection in mice. A significant amount of Hsp70 was also delivered to regional lymph nodes when it was injected subcutaneously, supporting the hypothesis that Hsp70 is a natural targeting system to APCs. Model antigens were complexed with or conjugated to Hsp70, by which greater antigen-specific immune responses were achieved. Cytoplasmic delivery of Hsp70-antigen further increased the efficacy of the Hsp70-based vaccines. These findings indicate that effective cancer therapy can be achieved by developing Hsp70-based anticancer vaccines when their tissue and intracellular distribution is properly controlled.
公益社団法人日本薬学会の論文
2007-02-01

体内・細胞内動態制御機能を搭載した熱ショックタンパク質の開発とワクチンデリバリーへの応用(誌上シンポジウム)

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