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获得较大量高细胞毒活性的LAK细胞,是LAK/IL-2继承性细胞免疫疗法的重要问题之一。为此我们进行了多年的实验研究,采用健康“O”型供血者外周血单个核细胞(PBMC)制备PHA-LAK细胞(即经PHA预刺激48小时然后用rIL-2诱导的LAK细胞),并与直接用rIL-2诱导的常规LAK细胞(C-LAK)的生物学特性进行了较全面的对比。结果发现PHA-LAK的增殖能力强,这与其IL-2R表达水平较高有关;同时PHA-LAK的细胞毒活性也高于常规LAK细胞。FACS表型分析表明:PHA-LAK的表型以CD_3~ⅠCD_8~Ⅰ为主,而常规LAK则以CD_3~ⅠNKH_1~Ⅰ为主,且PHA-LAK IL-2R的表达水平高于常规LAK。在此基础上,我们将PHA-LAK-/rIL-2应用于60例实体瘤患者的治疗,其中肾癌24例、恶性淋巴瘤5例、肝癌5例、肺癌12例、结肠癌5例及其它恶性肿瘤(包括膀胱癌、乳癌、胃癌、食道癌等)9例。
Obtaining a large amount of LAK cells with high cytotoxic activity is one of the important issues of LAK/IL-2 inherited cellular immunotherapy. To this end, we conducted many years of experimental studies, using healthy “O” donor peripheral blood mononuclear cells (PBMC) to prepare PHA-LAK cells (ie, LAK cells that were pre-stimulated with PHA for 48 hours and then induced with rIL-2), A more complete comparison was made with the biological characteristics of conventional LAK cells (C-LAK) induced directly with rIL-2. The results showed that PHA-LAK has a strong proliferative capacity, which is related to a higher level of IL-2R expression; meanwhile, the cytotoxic activity of PHA-LAK is also higher than that of conventional LAK cells. Phenotypic analysis of FACS showed that the phenotype of PHA-LAK is dominated by CD_3~ICD_8~I, while that of routine LAK is dominated by CD_3~INKH_1~I, and the expression level of PHA-LAK IL-2R is higher than that of conventional LAK. On this basis, we applied PHA-LAK-/rIL-2 to the treatment of 60 patients with solid tumors, including 24 cases of renal cell carcinoma, 5 cases of malignant lymphoma, 5 cases of liver cancer, 12 cases of lung cancer, and 5 cases of colon cancer. Other malignant tumors (including bladder cancer, breast cancer, stomach cancer, esophageal cancer, etc.) occurred in 9 cases.