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

本研究的目的是通过淋巴因子激活的杀伤细胞（LAK）与可识别肿瘤细胞表面抗原的嵌合性SF-25单克隆抗体（SF-25 Mab）连接，证明在裸鼠中建立的人结肠癌热处理对肿瘤细胞毒性的影响。将LS180人结肠腺癌细胞皮下注射到裸鼠体内，建立了人结肠癌模型。从健康志愿者的PBL制备LAK细胞，并通过聚乙二醇处理将SF-25单抗偶联至LAK细胞。然后，在热疗实验中，将一个热传感器置入肿瘤内，另一个热传感器置入对侧皮下，监测各部位的温度，然后进行红外线照射，在43.0℃的温度下对肿瘤区域进行加热，并证实红外线照射对小鼠非肿瘤区域没有加热作用。采用上述技术，将人结肠癌裸鼠分为：A组；小鼠用于注射与SF-25单抗结合的LAK细胞B组；C组为热疗组；单次注射与SF-25单抗结合的LAK细胞加热疗组为D组；注射与SF-25单抗结合的LAK细胞加热疗三次处理的小鼠，E组；未处理的对照小鼠。然后，监测肿瘤大小，以评估这些治疗的抗肿瘤效果。结果：1；与对照组相比，静脉注射与SF-25 Mab结合的LAK细胞可抑制小鼠的肿瘤生长，75%的处理小鼠无可检测到的肿瘤2。热处理小鼠肿瘤的发展速度比对照组快。注射与SF-25 Mab结合的LAK细胞加高温处理的小鼠与未处理的小鼠之间的肿瘤生长没有任何差异。

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.