Vose B M, Bonnard G D
Int J Cancer. 1982 Jan 15;29(1):33-9. doi: 10.1002/ijc.2910290107.
Peripheral blood lymphocytes of cancer patients were sensitized in vitro to autologous tumour cells in mixed lymphocyte-tumour culture (MLTC). Blast cells were isolated on discontinuous Percoll gradients from MLTC which showed significant stimulation of [3H]-thymidine incorporation. Cultured T cells (CTC) were derived from these blasts by growth in conditioned medium containing interleukin-2 (IL-2) and maintained for up to 51 days by repeated feeding with IL-2 and in some cases by addition of irradiated allogeneic blood mononuclear cells as "fillers". These cultures showed specific cytotoxic reactivity against autologous tumour and in only a few cases was natural killing (NK) of K562 cells apparent. Restimulation of CTC with tumour was measured in primed lymphocyte test (PLT). Increased uptake of [3H]-thymidine was found upon stimulation by autologous tumour and allogeneic tumour of the same site and histology but there was no response to non-related tumours or to a panel of allogeneic lymphocytes. No sensitization to autologous HLA-D/DR could be detected by restimulation or cytotoxicity against monocytes in the majority of cases. These data suggest that, by careful selection of sensitised blasts from MLTC, it is possible to obtain CTC with both helper (proliferative) and cytotoxic T cells and that such CTC have specific reactivity against tumour cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy.
癌症患者的外周血淋巴细胞在混合淋巴细胞 - 肿瘤培养(MLTC)中体外致敏于自体肿瘤细胞。在不连续的Percoll梯度上从MLTC中分离出母细胞,该MLTC显示出对[3H] - 胸腺嘧啶核苷掺入的显著刺激。培养的T细胞(CTC)通过在含白细胞介素 - 2(IL - 2)的条件培养基中生长从这些母细胞衍生而来,并通过反复添加IL - 2维持长达51天,在某些情况下通过添加经辐照的同种异体血单核细胞作为“填充剂”。这些培养物显示出对自体肿瘤的特异性细胞毒性反应,仅在少数情况下对K562细胞有明显的自然杀伤(NK)作用。在启动淋巴细胞试验(PLT)中测量了肿瘤对CTC的再刺激。发现自体肿瘤和相同部位及组织学的同种异体肿瘤刺激后[3H] - 胸腺嘧啶核苷摄取增加,但对无关肿瘤或一组同种异体淋巴细胞无反应。在大多数情况下,通过再刺激或对单核细胞的细胞毒性检测不到对自体HLA - D/DR的致敏。这些数据表明,通过仔细从MLTC中选择致敏母细胞,有可能获得同时具有辅助(增殖性)和细胞毒性T细胞的CTC,并且这种CTC对肿瘤细胞具有特异性反应性。这些细胞试剂将有助于确定人类肿瘤的抗原性,并可能用于治疗。