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[肿瘤浸润淋巴细胞(TIL)过继性免疫治疗肾细胞癌的研究——OKT3单克隆抗体增强白细胞介素-2诱导的TIL增殖]

[Study on adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) for renal cell carcinoma--amplification of IL-2-elicited TIL proliferation by OKT3-monoclonal antibody].

作者信息

Hayakawa M, Sisido S, Higa I, Koyama Y, Hatano T, Osawa A

机构信息

Department of Urology, School of Medicine, University of the Ryukyus.

出版信息

Nihon Hinyokika Gakkai Zasshi. 1990 Jan;81(1):103-9. doi: 10.5980/jpnjurol1989.81.103.

Abstract

Human autologous peripheral blood lymphocytes (PBL) and lymphocytes infiltrating renal cell carcinoma (TIL) were cultured with medium containing 1000 IU/ml of human interleukin 2 (IL-2). A high cytotoxic activity against fresh autologous as well as cultured allogenic tumor cells was developed. By culturing these lymphocytes with OKT3 monoclonal antibody during the initial 2 days of long-term culture, in terms of T cell activation signal, IL-2-driven lymphocyte proliferation was remarkably accelerated with maintenance of appreciable level of cytotoxic activity. The same culture method also induced an increase in OKT3 and IL-2 receptor positive lymphocyte population in LAK cells and TIL. This method may enable us to gain more autologous TIL in vitro for adoptive immunotherapy of renal cell carcinoma than the usual culture method with IL-2 alone. Five patients with metastatic renal cell carcinoma were treated with adoptive immunotherapy with TIL, LAK and IL-2. One patient with pulmonary metastasis has had a minor response which has lasted for 3 months so far. We have not experienced any serious side effects during the treatment.

摘要

将人自体外周血淋巴细胞(PBL)和浸润肾细胞癌的淋巴细胞(TIL)在含有1000 IU/ml人白细胞介素2(IL-2)的培养基中培养。针对新鲜自体以及培养的同种异体肿瘤细胞产生了高细胞毒性活性。在长期培养的最初2天,通过用OKT3单克隆抗体培养这些淋巴细胞,就T细胞激活信号而言,IL-2驱动的淋巴细胞增殖显著加速,同时保持了相当水平的细胞毒性活性。相同的培养方法还导致LAK细胞和TIL中OKT3和IL-2受体阳性淋巴细胞群体增加。与仅用IL-2的常规培养方法相比,这种方法可能使我们能够在体外获得更多用于肾细胞癌过继免疫治疗的自体TIL。5例转移性肾细胞癌患者接受了TIL、LAK和IL-2的过继免疫治疗。1例肺转移患者有轻微反应,迄今为止已持续3个月。治疗期间我们未经历任何严重副作用。

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