Antibody targeted CpG for the immunotherapy of solid tumors

A method is described to improve the therapeutic effects of unmethylated CpG oligodeoxynucleotides (ODNs) analogues, which can be used to stimulate the innate immune system for the treatment of cancer. The study is based on the generation of novel reagents that can be used to target tumors after linkage of CpG ODNs analogues to tumor-targeting monoclonal antibodies. This approach is novel in concept and may yield important information regarding the effectiveness of innate immunity in the treatment of cancer. CpG has been used primarily as an adjuvant injected locally at the site of interest or mixed with tumor vaccines. For systemic diseases such as cancer, however, the local administration of CpG would limit its potential to the site of injection. To address this, we have chemically linked active CpG motif analogues to chTNT-3, a monoclonal antibody which targets tumor necrosis, a site rich in tumor antigens. Our findings validate the usefulness of this novel approach and show that, compared to the parental antibody, the CpG immunoconjugate is able to target tumor and produce a 50% greater reduction in tumor growth. It is anticipated that the availability of antibody targeted CpG will enable research to optimize the effectiveness of this approach, especially when combined with other forms of immunotherapy, for the successful treatment of solid tumors. Additional studies using CpG motif analogues conjugated to rituximab (anti-CD20) and trastuzumab (anti-HER2/neu) are underway to demonstrate the full potential of this approach in tumors positive for these common biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1539. doi:1538-7445.AM2012-1539