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Clinical study on immunotherapy with lymphokine-activated killer cells for renal cancer.

淋巴因子激活杀伤细胞免疫治疗肾癌的临床研究。

基本信息

批准号：
62480339
负责人：
SONODA Takao
金额：
$ 4.48万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

In order to examine the utility of interleukin 2 (IL 2) to renal cancer as an immunotherapeutic agent, we used the method of a 4-hour ^<51>chromium-release cytotoxicity assay and showed that peripheral blood lymphocytes (PBLs) stimulated with IL 2 were capable of lysing autologous cultured tumor cells. This finding demonstrated the applicability of adoptive immunotherapy with lymphokine-activated killer (LSK) cells in RCC patients. In the present study, we carried out adoptive immunotherapy with autologous LAK cells in conjunction with systemic administration of IL 2 in patients with advanced RCC. Moreover, in order to investigate the possibility of selection of appropriate candidates for this immunotherapy on the basis of the results of a ^<51>chromium-release cytotoxicity assay employing autologous tumor cells as the target, we looked for a correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to the therapy.Eleven men and 3 women with metast … More atic rcc were entered in this study. They were aged between 37 and 72 years and had undergone nephrectomy for histologically proven RCC. A large number of lymphocytes (PBLs) were separated from lymphocyte-rich fraction obtained from leukaphereses by density centrifugation on ficoll-hypaque. The cells were suspended in 1000 or 2000 ml of RPMI 1640 containing 2 units/ml of IL 3, 50 ug/ml of gentamicin and 5% heat-inactivated human AD serum. After cultivation for 3-4 days, the IL 2-stimulated PBLs (LAK cells) were infused to the patients. In addition, 1000 units of IL 2 were infused once or twice a day. Of 14 patients, a partial response was observed in 3. As toxic symptoms, headache and shaking chills occurred immediately after each infusion of LAK cells. The toxic symptoms of IL 2 probably consisted of fever, edema and eosinophilia. The ^<51>chromum-release cytotoxicity assay employing autologous tumor cells as the target was performed in 6 of the 14 patients. Autologous tumor lysis in the 3 patients showing a partial response was 30.0%, 5.9% and 52.0%. On the other hand, the lung metastases did not respond to the therapy in spite of high autologous tumor cell lysis of more than 90%. Thus, no significant correlation was found between the in vitro assay and the clinical response.In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, particularly lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may risk increasing the frequency of brain metastases. Less

为探讨白细胞介素2（IL 2）作为免疫抑制剂对肾癌的作用，我们采用4小时铬<51>释放细胞毒试验方法，发现IL 2刺激的外周血淋巴细胞（PBL）能溶解自体培养的肿瘤细胞。这一发现证明了淋巴因子激活的杀伤（LSK）细胞过继免疫治疗在RCC患者中的适用性。在本研究中，我们进行了过继性免疫治疗与自体LAK细胞联合IL-2全身给药的晚期肾癌患者。此外，为了研究根据<51>以自体肿瘤细胞为靶点的铬释放细胞毒性试验结果选择合适的免疫治疗候选者的可能性，我们寻找了LAK细胞体外溶解自体肿瘤细胞与治疗临床反应之间的相关性。 ...更多信息本研究纳入了非典型RCC。他们的年龄在37至72岁之间，并接受了肾切除术的组织学证实的肾癌。通过在ficoll-hypaque上密度离心，从从白细胞去除术获得的富含淋巴细胞的级分中分离出大量淋巴细胞（PBL）。将细胞悬浮于1000或2000 ml含有2单位/ml IL 3、50 μ g/ml庆大霉素和5%热灭活人AD血清的RPMI 1640中。培养3- 4d后，将IL 2刺激的LAK细胞输注给患者。此外，每天输注1至2次IL 2 1000单位。在14例患者中，3例观察到部分缓解。毒性症状为每次输注LAK细胞后立即出现头痛和寒战。IL-2的毒性症状可能包括发热、水肿和嗜酸性粒细胞增多。在<51>14名患者中的6名中进行了使用自体肿瘤细胞作为靶标的β-染料释放细胞毒性测定。部分缓解3例，肿瘤自动溶解率分别为30.0%、5.9%和52.0%。另一方面，尽管自体肿瘤细胞溶解率高达90%以上，但肺转移瘤对治疗无反应。因此，没有显着的相关性，发现在体外试验和临床respons.In结论，虽然不能获得完全的反应，它可以说，这种免疫疗法可能是有效的对RCC，特别是肺转移，因为部分反应是在14例患者中的3例。然而，应该考虑到这种免疫方法可能会增加脑转移的频率。少