首页> 美国卫生研究院文献>Annals of Surgery >Melanoma-specific cytotoxic T cells generated from peripheral blood lymphocytes. Implications of a renewable source of precursors for adoptive cellular immunotherapy.
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Melanoma-specific cytotoxic T cells generated from peripheral blood lymphocytes. Implications of a renewable source of precursors for adoptive cellular immunotherapy.

机译:从外周血淋巴细胞产生的黑色素瘤特异性细胞毒性T细胞。可再生的前体来源对过继细胞免疫疗法的影响。

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摘要

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been generated in vitro from peripheral blood lymphocytes (PBL) of five patients with resectable stage II malignant melanoma. The PBL were cultured with 5u/ml recombinant IL-2 and were repeatedly stimulated with irradiated fresh or cultured autologous tumor cells. Cytotoxicity was determined by four-hour chromium release assays. Specific cytotoxicity developed in 30 to 40 days, after three or four stimulations with tumor. The PBL-derived CTL are CD3+ and are mixed for CD4+ and CD8+ phenotypes. They lysed autologous melanoma and failed to lyse allogeneic melanoma, K562, or autologous lymphocytes. The lysis of autologous tumor was maintained for more than 4 months. The cells proliferated in response to autologous, but not allogeneic melanoma cells, in a dose-dependent manner. Lysis of the autologous tumor target was inhibited with w6/32, a monoclonal antibody to HLA Class I antigens. It is concluded that PBL may serve as a plentiful and renewable source of precursor cells for the generation of autologous tumor-specific CTL, which may be useful in specific adoptive cellular immunotherapy of melanoma.
机译:从5名可切除的II期恶性黑色素瘤患者的外周血淋巴细胞(PBL)体外产生了对自体人类黑色素瘤具有特异性的细胞毒性T淋巴细胞(CTL)。用5u / ml重组IL-2培养PBL,并用经辐照的新鲜或培养的自体肿瘤细胞反复刺激。通过四小时的铬释放测定法测定细胞毒性。经过三到四次肿瘤刺激后,在30至40天内出现了特定的细胞毒性。 PBL衍生的CTL为CD3 +,并混合用于CD4 +和CD8 +表型。他们裂解了自体黑素瘤,但未能裂解同种异体黑素瘤,K562或自体淋巴细胞。自体肿瘤的裂解维持超过4个月。细胞以剂量依赖性方式响应自体而非异源黑素瘤细胞而增殖。用针对HLA I类抗原的单克隆抗体w6 / 32抑制自体肿瘤靶标的裂解。结论是,PBL可以作为前体细胞的大量可再生来源,用于自体肿瘤特异性CTL的产生,这可能在黑素瘤的特异性过继细胞免疫治疗中有用。

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