Production of fully human monoclonal antibodies to therapeutic self-antigenic targets (P3285)

• Published in: The Journal of immunology (1950) Vol. 190; no. 1_Supplement; pp. 192 - 192.28
• Main Authors: Sutkowski, Natalie, Sun, Wei, Fernandes, Daniel, Rubinchik, Semyon
• Format: Journal Article
• Language: English
• Published: 01.05.2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.192.28

Abstract Not all autoreactive antibodies are harmful, despite their role in autoimmune disease. Autoantibodies targeting tumor antigens, growth factors and their receptors are currently used therapeutically for treatment of cancer and autoimmunity. Ordinarily, healthy subjects do not exhibit strong secondary antibody responses to self-proteins, because most autoreactive B cells do not receive sufficient T cell help required for the germinal center reaction and for differentiation into IgG secreting cells. Our data demonstrate that rare, potentially therapeutic autoreactive B cells can be efficiently rescued from tonsil with EBV immortalization, and manipulated in vitro to secrete IgG, by supplying factors that mimic antigen stimulation and T cell help. Because this process is performed wholly in vitro, it constitutes a rapid and cost effective technology, resulting in the isolation of fully human antibodies. In addition, antibodies can be generated against highly toxic antigens, since immunization is unnecessary. As proof of concept, we have developed a panel of human monoclonal antibodies targeting the self-tumor antigen nucleolin for use in cancer immunotherapy. Nucleolin is normally expressed in the nucleus of all cells, but it is over-expressed in both the cytoplasm and on the cell surface of tumor cells in the most common forms of breast cancer, making nucleolin a new type of tumor antigen. The antibodies are currently undergoing pre-clinical testing against breast cancer.