AR53A10.11 and AR58A314.1, 2 ARIUS functional monoclonal antibodies target tumor specific antigens

637 A potential benefit of targeted therapies in oncology is their ability to distinguish cancerous tissue from healthy tissue. It is possible to generate cancer-specific antibodies using known tumor related antigens but functionality, i.e. intrinsic biological activity beyond binding, is not predictable. By using the FunctionFIRST™ antibody generation platform, 2 functional antibodies targeting tumor specific antigens were produced from patient tumor tissues and screened for differential anti-tumor activity. AR53A10.11 and AR58A314.1 have selective cytotoxicity for cancer cells in vitro and efficacy against common human cancers in vivo . AR53A10.11 is an IgG2 monoclonal antibody raised against human ovarian cancer. The antibody showed cytotoxicity to DLD-1 colon cancer cells line and no binding by FACS or cytotoxicity to normal cell lines in vitro . In a preventative DLD-1 human colon cancer xenograft model in SCID mice, the antibody showed significant suppression of DLD-1 xenograft growth, where the average tumor sizes were 38.6% (p in vitro . In a preventative A549 human lung cancer and BxPC3 human pancreatic cancer xenograft models in SCID mice, the average tumor sizes in the antibody-treated groups were 51.4 % and 54.2% of the buffer treated groups, respectively. Immunohistochemistry analysis was carried out in a small group of human normal and cancer frozen tissues to determine the distribution of the antigens for the 2 antibodies. Both antibodies bound with a clear differential to human cancer samples of colon, breast, lung and prostate compared to normal human tissue sections. AR53A10.11 showed binding to 4/4 of colon, breast, lung and prostate cancers available on the tissue microarray with no binding to their corresponding normal tissues with the exception of prostate. AR58A314.1 showed binding to 1/4 of colon and 2/4 of lung cancers with no binding to any of the tested normal tissues. There is early evidence that the functional monoclonal antibodies AR53A10.11 and AR58A314.1 target tumor specific antigens and may be used as naked antibodies or conjugated to other anticancer agents.