Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma

被引:174
作者
Wooldridge, JE
Ballas, Z
Krieg, AM
Weiner, GJ
机构
[1] UNIV IOWA,COLL MED,IOWA CITY VET ADM,IOWA CITY,IA
[2] UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA
[3] UNIV IOWA,COLL MED,GRAD PROGRAM IMMUNOL,IOWA CITY,IA
关键词
D O I
10.1182/blood.V89.8.2994
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:2994 / 2998
页数:5
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