Natural IgG antibodies as therapeutic agents for carcinoma and melanoma

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 2128 Natural or innate immunity is the first line defence against cancer. Antibodies play a major role in these processes and the majority of these germ-line coded antibodies are pentameric IgMs. Several of these natural antibodies have already been successfully used in clinical trials and for definition of new cancer targets. Natural immunity is also the bridge to immunological memory, resulting in affinity maturated IgG antibodies. We used the human hybridoma technology to screen cancer patients in a huge study on the humoral immune response for tumor-specific IgGs. Interestingly, we were able to isolate not only many cancer specific IgM antibodies, but also several tumor-reacting IgGs. We show in this study that these monomeric immunoglobulins show specific binding to carcinoma and melanoma cells, inhibit proliferation and induce apoptosis, similar to the already characterized natural IgMs. However, when sequenced, all found IgGs are not affinity-maturated. Biochemical studies on the antigens are underway. Natural IgG antibodies have been detected in sera, in quantities less than 1%, but so far, no one has been isolated, established and characterized in detail. This is the first report on natural monoclonal IgG antibodies with anti-cancer activity.