Liang Zhi-Ping, Liu Chang-Zheng, Cheng Jing-Yi, Xiao Xi-Bin, Zhang Chang-Qing, Liang Chang-Sheng
Department of Experimental Nuclear Medicine, Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou, Guangdong, 510080, PR China.
Ai Zheng. 2003 Aug;22(8):831-5.
BACKGROUND & OBJECTIVE: Combined therapy has been advocated for modern tumor treatment; the combined target therapy is a valuable research direction. Based on the previous research of nasopharyngeal carcinoma (NPC) radioimmunotherapy, this experiment was designed to develop two immunoconjugates of the monoclonal antibody BAC(5):PYM-BAC(5) and (131)I-BAC(5), and to assess the inhibition effects of their combined treatment on the NPC CNE-2 cells cultured in vitro.
Dextran T40 was used as media to link PYM and BAC(5). The conjugate PYM-BAC(5) was identified by testing its immunoactivity and the inhibition to mycobacterium. BAC(5) was labeled with (131)I by Chloramin-T method. Five experimental groups were set up:(1)PYM-BAC(5) group, (2)free PYM group, (3)(131)I-BAC(5) group, (4)(131)I-mIgG group, (5)the combined target treatment group ( (131)I-BAC(5)+PYM-BAC(5)). The antitumor effects of the five groups were assessed with MTT method.
The 50% inhibition doses(IC(50)) of PYM-BAC(5) group and PYM group were 46.57 microg/ml and 316.7 microg/ml, respectively. The IC(50) of (131)I-BAC(5) group and (131)I-mIgG group to CNE2 were 4.42 x 10(5) Bq/ml and >11.1 x 10(5) Bq/ml,respectively. In the combined target treatment group(PYM-BAC(5)+(131)I-BAC(5)),the IC(50) of PYM-BAC(5) was 7.01 microg/ml and of (131)I-BAC(5) was 0.54 x 10(5) Bq/ml, which much less than other separate treatment groups.
The inhibition effects of the target treatment ((131)I-BAC(5) and PYM-BAC(5)) on the NPC CNE-2 cells are stronger than non-target treatment (free PYM and (131)I-BAC(5)). The combined target treatment of the two immune ((131)I-BAC(5)+PYM-BAC(5)) conjugates gets stronger inhibition effects than their separate treatment.
联合治疗一直是现代肿瘤治疗所倡导的方法;联合靶向治疗是一个有价值的研究方向。基于既往鼻咽癌放射免疫治疗的研究,本实验旨在研制两种单克隆抗体BAC(5)的免疫偶联物:PYM-BAC(5)和(131)I-BAC(5),并评估它们联合治疗对体外培养的鼻咽癌CNE-2细胞的抑制作用。
以葡聚糖T40为介质连接PYM和BAC(5)。通过检测其免疫活性及对分枝杆菌的抑制作用对偶联物PYM-BAC(5)进行鉴定。采用氯胺-T法用(131)I标记BAC(5)。设立5个实验组:(1)PYM-BAC(5)组;(2)游离PYM组;(3)(131)I-BAC(5)组;(4)(131)I-鼠IgG组;(5)联合靶向治疗组((131)I-BAC(5)+PYM-BAC(5))。采用MTT法评估5组的抗肿瘤作用。
PYM-BAC(5)组和PYM组的50%抑制浓度(IC(50))分别为46.57μg/ml和316.7μg/ml。(131)I-BAC(5)组和(131)I-鼠IgG组对CNE2的IC(50)分别为4.42×10⁵Bq/ml和>11.1×10⁵Bq/ml。在联合靶向治疗组(PYM-BAC(5)+(131)I-BAC(5))中,PYM-BAC(5)的IC(50)为7.01μg/ml,(131)I-BAC(5)的IC(50)为0.54×10⁵Bq/ml,均远低于其他单独治疗组。
靶向治疗((131)I-BAC(5)和PYM-BAC(5))对鼻咽癌CNE-2细胞的抑制作用强于非靶向治疗(游离PYM和(131)I-鼠IgG)。两种免疫偶联物((131)I-BAC(5)+PYM-BAC(5))联合靶向治疗的抑制作用强于单独治疗。