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    • 16. 发明申请
    • METHOD FOR USING PEPTIDE COMPLEXES/MAJOR HISTOCOMPATIBILITY COMPLEX TO OBTAIN OR PURIFY ANTIGEN-SPECIFIC T CELLS AND TO STIMULATE T CELLS
    • 使用肽复合物/主要组氨酸复合物获得或纯化抗原特异性T细胞并刺激T细胞的方法
    • WO1997044667A2
    • 1997-11-27
    • PCT/FR1997000892
    • 1997-05-21
    • INSTITUT PASTEURINSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)LANGLADE-DEMOYEN, PierreLONE, Yu-ChunKOURILSKY, PhilippeABASTADO, Jean-Pierre
    • INSTITUT PASTEURINSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
    • G01N33/569
    • C07K14/005C07K14/70539C12N2760/16122G01N33/56977G01N33/574
    • The invention features methods for using MHC/peptide complexes. The successful peptide-specific T lymphocyte purification by adsorption on a solid support coupled with a high density of MHC recombinant molecules, charged with a single peptide is disclosed. This method has enabled the isolating, purifying and quantifying of tumoral specific T lymphocytes, from peritoneal exudate and tumor-infiltrating lymphocytes. These purified T lymphocyte populations can be further multiplied in vitro. The resulting cells show a superior cytotoxic activity and an enhanced anti-tumoral action by re-injection in the tumor carrier. This novel approach is important for analysing the T lymphocytes repertoire at the peptide specificity level and to improve novel T lymphocyte adoptive immunotherapy based therapeutic treatments. Further, the MHC/peptide specific complexes can induce or stimulate peptide-specific T lymphocytes. Thus are also disclosed methods to induce cytotoxic T lymphocytes (CTL). These CTL can be used in turn to fight tumoral cell growth in vitro or in vivo. The MHC recombinant molecule charged with a single peptide can be effectively used in polymer form to stimulate specific immune response ex vivo or in vivo after being injected in man or animal.
    • 本发明的特征在于使用MHC /肽复合物的方法。 公开了通过在固体支持物上吸附成功的肽特异性T淋巴细胞,其与高密度的MHC重组分子偶联,装载有单一肽。 该方法能够从腹膜渗出液和肿瘤浸润淋巴细胞中分离,纯化和定量肿瘤特异性T淋巴细胞。 这些纯化的T淋巴细胞群可以进一步在体外倍增。 所得细胞通过在肿瘤载体中重新注射显示出优异的细胞毒性活性和增强的抗肿瘤作用。 这种新方法对于分析肽特异性水平的T淋巴细胞谱和改善基于T淋巴细胞过继免疫治疗的治疗方法是重要的。 此外,MHC /肽特异性复合物可以诱导或刺激肽特异性T淋巴细胞。 因此,还公开了诱导细胞毒性T淋巴细胞(CTL)的方法。 这些CTL可以依次用于在体外或体内抗肿瘤细胞生长。 带有单个肽的MHC重组分子可以有效地以聚合物形式使用,以便在人或动物注射后离体或体内刺激特异性免疫应答。