权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of Culture system for LAK cells and its application to adoptive immunotheraphy for lung cancer.

LAK细胞培养系统的开发及其在肺癌过继免疫治疗中的应用。

基本信息

批准号：
02557049
负责人：
KIMURA Genki
金额：
$ 11.46万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02557049/
关键词：
LAK cell LIFROC culture apparatus Liquid-filled rotatory culture Lymphokine-activated killer cell Adopted immunotheraphy Lymphocyte culture High-density cell culture Lung cancer LAK細胞肺癌術後補助療法高密度培養回転培養養子免疫療法インターロイキン2 LAT

项目摘要

For application with surgical adjuvant therapy of cancer. we have designed a unique regimen of adopuve immunotherapy with lymphokineacuvated killer (LAK) cells and recombinant interleukin-2 (IL-2). The regimen features the prolonged (6 consecutive days) subcutaneous administration of a low-dose IL-2 and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of operations. According to this regimen. 19 patients with pathological stage-1 lung cancer received immunotheraph about 2 weeks after pulmonary lobectomy. Clinical toxicities included fever. fatigue. <5% weight gain. and edema.All toxicities reversed within 4 days after the complection of therapy. In 13 patients. peripheral blood lymphecytes obtained 24h after therapy exhibited in vitro LAK activity. Thus the regimen is considered to be well-tolerable and immunologically active, in regard to the postoperative state of the patients.To improve the routine performance of the generation and expansion of LAK cells. we have developed a new culture system (LIFROC Liquid-Filled Rotary Culture : formaly designated JCC device). The LIFROC system is essentially based on dialysis culture. A dialysis membrane divides the culture vessel from the outside circulation of basal medium. The culture vessel is rotated for the proper dispersion of cells and supplied with oxygen through a silicon tube.With this LIFROC system. the cell density reached a maximum 2.7x10^7 cells/ml with greater than 90% viability and a substantial level of LAK activity. In comparison with a convenstonal batchwise culture system suing tissue culture dishes. the LIFROC system was able to reduce the consumption of basal medium. IL-2. and serum by 20%, 84%, and96%, respectively.Culture vessel, reservoir, and tools for the recovery of LAK cells from culture medium were devised to be disposable. This culture system is apphed with safe to culture LAK cells for adoptive immunotheraphy.

用于癌症的外科辅助治疗。我们设计了一种独特的过继免疫治疗方案，使用淋巴动激活杀伤细胞（LAK）和重组白细胞介素-2 （IL-2）。该方案的特点是延长（连续6天）皮下给药低剂量IL-2，并转移手术时获得的区域淋巴结淋巴细胞体外生成的LAK细胞。按照这个养生法。病理1期肺癌19例在肺叶切除术后约2周接受免疫治疗。临床毒性包括发热。乏力。体重增加<5%。和水肿。所有毒性在治疗结束后4天内逆转。13个病人。治疗24h后获得的外周血淋巴细胞显示体外LAK活性。因此，考虑到患者的术后状态，该方案被认为具有良好的耐受性和免疫活性。提高LAK细胞的生成和扩增的常规性能。我们开发了一种新的培养系统（LIFROC液体填充旋转培养：正式命名为JCC设备）。LIFROC系统本质上是基于透析培养。透析膜将培养管与基础培养基的外部循环分隔开。将培养容器旋转以使细胞适当分散，并通过硅管提供氧气。使用这个LIFROC系统。细胞密度最大达到2.7 × 10^7个/ml，存活率大于90%，LAK活性较高。与使用组织培养皿的传统分批培养系统进行比较。LIFROC系统能够减少基础介质的消耗。- 2。血清分别减少20%，84%和96%培养容器、储液器和从培养基中回收LAK细胞的工具设计为一次性的。该培养体系可安全用于LAK细胞的过继免疫治疗。