Innate immunity and cancer : Genetics , specificity and function of natural monoclonal IgM antibodies

Innate immune mechanisms are crucial for first defense and initiation of secondary responses to “nonself” structures. This has been shown for bacterial antigens, but the recognition and defence-activity against malignant cells is still obscure. By using human hybridoma-technology we have isolated hundreds of human monoclonal antibodies from different patients with different tumours. All of these antibodies are of IgM type, none of them was an affinity-maturated IgG or IgA type. We have sequenced several of these antibodies and have characterised binding pattern and determined origin and genetics. It was found that all IgM antibodies are not or only less mutated (germ-line coded), and bind to carbohydrates on modified tumourspecific receptors (DAF, CFR-1). The degree of crossreactivity to other tumours correlates with the grade of mutations in coding regions. By using an anti-idiotypic antibody, we could show, that the IgM-producing cells are CD5 positive. The striking similarities between the humoral response to bacteria and tumor cells, presented here, makes it likely that the same or similar recognition and defense mechanisms are used. Origin, reactivity pattern and genetics of these real tumor-specific antibodies are close to that what we know from the defense to bacterial structures and it is likely that innate imunity is not only resposible for recognition and elimination of bacterial structure but also for removal of malignant cells. [16.45–17.05] A human monoclonal antibody (HMMC-1) that selectively recognizes müllerian duct-related carcinomas Atsushi Suzuki , Shiro Nozawa, Daisuke Aoki , Katsumi Tsukazaki , Nobuyuki Susumu , Motoko Sakayori , Nao Suzuki , Makio Mukai, Kyoko Kojima-Aikawa, Michiko N. Fukuda and Isao Ishida Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan Division of Diagnostic Pathology, School of Medicine, Keio University, Tokyo, Japan Department of Chemistry, Faculty of Science, Ochanomizu University, Tokyo, Japan Glycobiology Department, The Burnham Institute, La Jolla, CA, USA Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan