ARIUS has generated functional antibodies to novel cancer antigens which are effective against breast cancer and melanoma in vitro and in vivo. Current results describe the prevalence of antigens for these antibodies in surveys of human breast and melanoma cancer sections, and demonstrate that these antibodies target a population separate from those served by anti-Her2/neu antibodies and each other. Two ARIUS antibodies, ARH460-16-2 and AR7BD-33-11A (targeting CD44 and CD63, respectively) significantly suppress and delay tumor growth and increase survival in a xenograft model of Her2/neu-negative breast cancer. Distribution of the ARH460-16-2 and AR7BD-33-11A antigens in breast cancer was determined by the immunohistochemistry of breast cancer sections from 50 individual patients in an array format. Findings were compared to those for an anti-Her2/neu polyclonal antibody from Dako commonly used to assess Her2/neu status. Of the 55% of Her2/neu negative sections, 23% expressed antigens for ARH460-16-2 or AR7BD-33-11A only, while a further 15% expressed the antigen for both ARIUS antibodies, but not Her2/neu. Only 17% of breast cancer sections were negative for all three antigens. In addition, 28% of sections expressed Her2/neu along with epitopes for one or both ARH460-16-2 and AR7BD-33-11A. In melanoma, anti-CD63 antibodies and AR11BD-2E11-2 (directed against melanoma-associated chrondroitin-sulphate proteoglycan; MCSP) suppressed tumor growth in prophylactic and established xenograft models. Immunohistochemistry using frozen human melanoma sections revealed that 9% of the sections expressed only MCSP, 12% expressed CD63, 58% expressed both antigens, and 21% expressed neither. Antibodies to MCSP and CD63 may target up to 80% of the melanoma patient population. In the examples above, each cancer may express combinations of targets suggesting potential for additive therapeutic effects through independent mechanisms of action and offering a rationale for combined antibody therapy in selected patients.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]