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Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the
efficacy of monoclonal antibody therapy of lymphoma
JE Wooldridge, Z Ballas, AM Krieg and GJ Weiner
Iowa City Veterans Administration, the Department of Internal Medicine, The
University of Iowa College of Medicine, USA.
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 tumor
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.
Volume 89,
Issue 8,
pp. 2994-2998,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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