CD_3单克隆抗体加白细胞介素2活化的杀伤T细胞系治肿瘤的安全性

Safety of biotherapy of tumor with CD_3McAb plus IL-2 activated killer T cell line

目的 :探讨CD3单克隆抗体 (CD3McAb)与小剂量白细胞介素 2 (IL 2 )活化的杀伤T细胞系治疗肿瘤病人的安全性。方法 :从健康人外周血、脐血、人胎胸腺或病人自体血分离淋巴细胞 ,经诱导、激活传代后获淋巴因子活化的杀伤细胞 (LAK)和CD3AK细胞系 ,先分别试用 10例病人 ,(1～ 5 )×10 8,iv ,每个疗程 5次 ,显示安全有效后增加病例 ,LAK细胞组 5 0例 ,CD3AK细胞组 4 0例。结果 :效应细胞生长形态良好 ,多数能长出细胞集落。生长曲线表明CD3AK细胞比LAK细胞增殖快 ,生长时间长 ;CB CD3AK和PBL CD3AK细胞对数生长期为d 9～ 18,能从 10 6 扩增到 10 8,而其他细胞对数生长期为d 6～ 15 ,扩增到 10 7,110例病人经iv 5 48次治疗 ,不良反应主要为发热和寒颤 ,偶有恶心、呕吐 ,眩晕 ,皮疹 ;HFT LAK发生率为 11% ,其他约 5 % ,CD3AK平均不良反应发生率为 3.6 %。结论 :CD3McAb与小剂量IL 2活化的杀伤T细胞系可以安全地用于治疗肿瘤。

AIM: To investigate the safety in treating tumor patients with CD 3McAb plus low dose of IL-2 activated killer (CD 3AK) cell line. METHODS:Precursor lymphocytes were separated from healthy human peripheral blood or cord lymphocytes or human fetal thymus (HFT) or patients peripheral blood. LAK cells were induced with complete medium plus IL-2(2-2.5)×106U·L -1,CD 3AK was activated with complete medium plus IL-2 (5-10)×105U·L -1 and CD 3McAb 4-10 mg·L -1, then subcultured to establish cell line. LAK and CD 3AK cell line were harvested, and a trial of ten patients infused intravenously was performed, respectively. Adverse reactions were defined by WHO criteria. It was safe and effective for the patients to accept (1-5)×108 cells each infusion, five infusions one course. Then increasing patients:fifty patients in LAK treatment group, forty patients in CD 3AK treatment group. RESULTS:These effectors grew well in morphology, and most precursor lymphocytes could form cell colonies. The growth curve showed that CD 3AK cell line could proliferate faster and grew longer than LAK; the logarithmic growing phase of CD 3AK from healthy human peripheral blood or cord lymphocytes was 9 to 18 of culture, expanding from 106 to 108, however, other effectors logarithmic growing phase was d 6 to d 15 of culture, only to 107. One hundred and ten patients accepted a total of 548 infusions via iv. More adverse reactions were fever and shivering, on occasion, nausea and vomiting, dizziness, rash could be observed. The rate of adverse reactions in HFT-LAK reached 11 %, others about 5 %; the mean rate of adverse reactions in 250 CD 3AK infusions of 50 patients was 3.6 %. CONCLUSION:CD 3McAb plus low dose of IL-2 activated killer T cell line can be used safely in therapy of tumor.