Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma
Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma
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DOI：
10.1182/blood.v89.8.2994
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发表时间：
1997-04-15
期刊：
影响因子：
20.3
通讯作者：
Weiner, GJ
中科院分区：
文献类型：
--
作者：
Wooldridge, JE;Ballas, Z;Weiner, GJ
细菌DNA和含有CpG基序的合成寡脱氧核苷酸（CpG ODN）可以激活各种免疫细胞亚群，包括自然杀伤细胞和巨噬细胞。我们评估了CpG ODN和抗肿瘤单克隆抗体的组合是否能有效地阻止免疫活性小鼠淋巴瘤模型中的turner生长。CpG odn激活的小鼠脾细胞比未激活的脾细胞更有效地诱导肿瘤靶点的溶解。这些效应细胞在诱导抗体介导的38C13小鼠淋巴瘤细胞裂解方面也优于未活化的脾细胞或对照甲基化ODN活化的细胞。在体内，单独注射CpG ODN对38C13细胞接种小鼠的存活无影响，而单次注射CpG ODN可增强小鼠对抗肿瘤单克隆抗体治疗的抗肿瘤反应。单独使用单克隆抗体治疗的小鼠中90%发生肿瘤，而使用抗体和CpG ODN治疗的小鼠中只有20%发生肿瘤。当治疗由含有甲基化CpG二核苷酸的相同ODN组成时，这些抗肿瘤作用不那么明显。当与抗肿瘤单克隆抗体联合使用时，单剂量CpG ODN在抑制肿瘤生长方面与多剂量白介素-2一样有效。我们得出结论，免疫刺激CpG ODN可以增强抗体依赖的细胞毒性，值得进一步评估作为潜在的癌症免疫治疗试剂。(C) 1997年由美国血液病学会出版。
Bacterial DNA and synthetic oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets, including natural killer cells and macrophages. We evaluated whether the combination of CpG ODN and antitumor monoclonal antibody is effective at preventing turner growth in an immunocompetent murine lymphoma model. CpG ODN-activated murine splenocytes induced lysis of tumor targets more effectively than unactivated splenocytes. These effector cells were also superior to unactivated splenocytes or cells activated with a control methylated ODN at inducing antibody-mediated lysis of 38C13 murine lymphoma cells. In vivo, CpG ODN alone had no effect on survival of mice inoculated with 38C13 cells, However, a single injection of CpG ODN enhanced the antitumor response to antitumor monoclonal antibody therapy. Ninety percent of mice treated with monoclonal antibody alone developed tumor compared with 20% of mice treated with antibody and CpG ODN. These antitumor effects were less pronounced when treatment consisted of an identical ODN containing methylated CpG dinucleotides. A single dose of CpG ODN appeared to be as effective as multiple doses of interleukin-2 at inhibiting tumor growth when combined with antitumor monoclonal antibody, We conclude that immunostimulatory CpG ODN can enhance antibody dependent cellular cytotoxicity and warrant further evaluation as potential immunotherapeutic reagents in cancer. (C) 1997 by The American Society of Hematology.