IMMUNOSTIMULATORY OLIGODEOXYNUCLEOTIDES CONTAINING CPG MOTIFS ENHANCETHE EFFICACY OF MONOCLONAL-ANTIBODY THERAPY OF LYMPHOMA

Bacterial DNA and synthetic oligodeoxynucleotides containing the CpG m otif (CpG ODN) can activate various immune cell subsets, including nat ural killer cells and macrophages. We evaluated whether the combinatio n of CpG ODN and antitumor monoclonal antibody is effective at prevent ing turner growth in an immunocompetent murine lymphoma model. CpG ODN -activated murine splenocytes induced lysis of tumor targets more effe ctively than unactivated splenocytes. These effector cells were also s uperior to unactivated splenocytes or cells activated with a control m ethylated ODN at inducing antibody-mediated lysis of 38C13 murine lymp homa cells. In vivo, CpG ODN alone had no effect on survival of mice i noculated with 38C13 cells, However, a single injection of CpG ODN enh anced the antitumor response to antitumor monoclonal antibody therapy. Ninety percent of mice treated with monoclonal antibody alone develop ed 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 inter leukin-2 at inhibiting tumor growth when combined with antitumor monoc lonal antibody, We conclude that immunostimulatory CpG ODN can enhance antibody dependent cellular cytotoxicity and warrant further evaluati on as potential immunotherapeutic reagents in cancer. (C) 1997 by The American Society of Hematology.