EFFECT OF HEAT TREATMENT TO HUMAN COLON CANCER ON CYTOTOXICITY OF LYMPHOKINE-ACTIVATED KILLER CELLS LINKED WITH TUMOR SPECIFIC MONOCLONAL ANTIBODIES TO THIS TUMOR IN NUDE MOUSE MODEL

裸鼠模型中人类结肠癌热处理对与该肿瘤特异性单克隆抗体相关的淋巴因子激活杀伤细胞的细胞毒性的影响

• 批准号: 08670535
• 负责人: NAKADA Tetsuya
• 金额: $ 0.51万
• 依托单位: THE JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670535/
• 关键词: LAK cell; LAK activity; Monoclonal antibody; Hyperthermia; Tumor immunology; Cancer; Nude mouse

The aim of this study is to demonstrate the effect of heat treatment of human colon cancer established in nude mice on the cytotoxicity to this tumor by lymphokine-activated killer (LAK) cells linked with chimeric SF-25 monoclonal antibodies (SF-25 Mab) which can recognize a tumor cell surface antigen. Subcutaneous injection of LS180 human colon adenocarcinoma cells into nude mice establishes in these mice a model for human colon cancer. LAK cells were Prepared from PBL of healthy volunteer and SF-25 Mabs were conjugated to LAK cells by polyethylene glycol treatment. Then, for the experiment of hyperthermia, the one thermosensor was placed in the tumor and the other one was inserted into subcutaneous region of opposite site to monitor the temperature at each area, then irradiation of infrared rays were performed in order to heat the tumor area at 43.0ﾟC and also confirmed that irradiation of infrared rays did not heat the non-tumor region of mouse. Using these techniques, human colon cancer bearing nude mice were assigned to as follows : group A ; the mice for the injection of LAK cells conjugated to SF-25 Mab, group B ; the mice for the hyperthermia, group C ; the mice for the single treatment with injection of LAK cells conjugated to SF-25 Mab plus hyperthermia, group D ; the mice for the three time treatments with injection of LAK cells conjugated to SF-25 Mab plus hyperthermia, group E ; non-treated control mice. Then, the tumor size were monitored to evaluate the anti-tumor effects of these treatments.Results : 1.The intravenous injection of LAK cells conjugated to SF-25 Mab into mice inhibited the tumor growth compared to that of the control group, and 75% of the treated mice were free of detectable tumor.2.The heat treated mice developed tumor more rapidly than control mice.3.There were not any difference in the growth of tumor between the mice treated with injection of LAK cells conjugated to SF-25 Mab plus hyperthermia and non-treated mice.

本研究的目的是证明热处理在裸鼠中建立的人结肠癌对与嵌合SF-25单克隆抗体（SF-25 Mab）连接的淋巴因子激活的杀伤（LAK）细胞对该肿瘤的细胞毒性的影响，该嵌合SF-25 Mab可以识别肿瘤细胞表面抗原。将LS 180人结肠腺癌细胞皮下注射到裸鼠中，在这些小鼠中建立人结肠癌模型。从健康志愿者的外周血淋巴细胞中制备LAK细胞，通过聚乙二醇处理将SF-25单克隆抗体与LAK细胞偶联。然后，对于热疗实验，将一个温度传感器放置在肿瘤中，另一个插入相对部位的皮下区域以监测每个区域的温度，然后进行红外线照射以将肿瘤区域加热到43.0 ° C，并且还证实红外线照射不会加热小鼠的非肿瘤区域。将荷人结肠癌裸鼠随机分为A组、SF-25 MaB结合LAK细胞注射组（B）、热疗组（C）、SF-25 MaB结合LAK细胞注射+热疗组（D）、热疗组（D）和热疗组（D）。E组：注射SF-25单抗标记的LAK细胞并加温治疗3次;对照组：未治疗。然后，监测肿瘤大小以评估这些治疗的抗肿瘤效果。1.静脉注射SF-25单克隆抗体标记的LAK细胞对荷瘤小鼠的肿瘤生长有明显的抑制作用，以及75%热处理组小鼠的肿瘤生长速度明显快于对照组小鼠结果：经SF-25单抗标记的LAK细胞联合热疗治疗的小鼠与未经治疗的小鼠之间的肿瘤转移率差异无统计学意义。