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Methods of preparing lymphocytes that express interleukin-2 and their use in the treatment of cancer

机译:表达白介素2的淋巴细胞的制备方法及其在癌症治疗中的应用

摘要

A method of preparing autologus T-lymphocytes for re-introduction into a patient having cancer, which method comprises obtaining peripheral blood mononuclear cells (PBMCs) from a patient immunized with an antigen of the canncer, stimulating the PBMCs with the antigen of the cancer in vitro, transducing the PBMCs with a retrovial vector, which (a) comprises and expresses a human interleukin-2 (IL-2) coding sequence operably linked to a retroviral promoter, (b) does not comprise an exogenously introduced gene that enables phenotypic selection, and (c) comprises a viral envelope that efficiently transduces CD8+ T-lymphocytes; a method of preparing autologous tumor-infiltrating lymphocytes (TILs) for reintroduction into a patient having cancer, which method comprises obtaining TILs from a tumor of the patient, optionally immunized with an antigen of the cancer, optionally stimulating the TILs with the antigen of the cancer in vitro, and transducing the TILs with the aforementioned retroviral vector; compositions comprising cells obtained in accordance with such methods; and methods of treating a patient having cancer by administering to the patient cells obtained in accordance with such methods or compositions comprising same.
机译:一种制备自体T淋巴细胞以重新引入患有癌症的患者的方法,该方法包括从用癌的抗原免疫的患者获得外周血单核细胞(PBMC),用癌症的抗原刺激PBMC。在体外,用逆转录病毒载体转导PBMC,该载体(a)包含并表达与逆转录病毒启动子可操作连接的人白介素2(IL-2)编码序列,(b)不包含能够进行表型选择的外源导入基因(c)包含有效转导CD8 + T淋巴细胞的病毒包膜;一种制备自体肿瘤浸润淋巴细胞(TIL)以重新引入患有癌症的患者的方法,该方法包括从患者的肿瘤获得TIL,任选地用癌症的抗原免疫,任选地用肿瘤的抗原刺激TIL。体外癌症,并用上述逆转录病毒载体转导TIL;包含根据这种方法获得的细胞的组合物;通过将根据这种方法或包含其的组合物获得的细胞给予患者,来治疗患有癌症的患者的方法和方法。

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