肿瘤抗原 CTL 表位修饰策略研究进展

摘要

肿瘤抗原 CTL 表位能诱导特异性的细胞毒性 T 淋巴细胞（cytotoxic T lymphocyte，CTL）杀伤肿瘤细胞，但是单一表位存在分子量小、免疫原性低等缺点。表位修饰可增加其分子量，提升其免疫原性，诱导更有效的肿瘤杀伤效应。CTL 表位修饰包括表位分子氨基酸残基的改造和引入修饰分子。改造天然表位的氨基酸残基改变了表位分子的氨基酸序列，但保留其特异的抗原性，并可提高表位呈递效率。常用的 CTL 表位修饰分子包括 Toll 样受体配体、C 型凝集素受体特异性抗体、β2微球蛋白、病毒样蛋白微粒等，其可改变表位构象，但保留表位特异的抗原性，提高表位呈递的靶向性，且能诱导特异性高、强度大的免疫反应。本文将对表位修饰的具体策略作一简要综述。%CTL epitopes of tumor antigens are able to induce specific tumor cell killing cytotoxic T lymphocytes,but they are with the deficiency of low immunogenicity.Modification of CTL epitopes is a way to enhance its immunogenic-ity,inducing T cells to kill tumor cells more effectively.The modification of CTL epitopes includes alteration of amino residues of the epitopes and introduction of modification molecules.Epitopes with altered amino acid sequence give rise to high and sustained cross -presentation,meanwhile share similar specific antigenicity with wild -type epitopes. Various molecules can be introduced to enhance the immunogenicity of wild -type epitopes,with the consequence of conformational changes but superior in targeting property of cross -presentation and eliciting stronger tumor antigen -specific immune response.Those commonly used are Toll -like receptor ligands,antibodies of C -type lectin recep-tors,β2 microglobulins and virus -like particles.Here we summarize the strategies of tumor CTL epitopes modifica-tion.