The antitumor activity of an anti-CD54 antibody in SCID mice xenografted with human breast, prostate, non-small cell lung, and pancreatic tumor cell lines

We have previously described the development and testing of a monoclonal anti-human CD54 antibody (UV3) in SCID mice xenografted with human multiple myeloma, lymphoma, and melanoma cell lines. In all 3 cases, UV3 was highly effective at slowing the growth of tumors and/or prolonging survival. Since CD54 (ICAM-1) is up-regulated on many different types of cancer cells, we have now investigated the anti-tumor activity or UV3 in several other CD54(+) epithelial tumors. A panel of I human breast, prostate, non-small cell (NSC) lung, and pancreatic tumor cell lines was examined for reactivity with UV3, and 13 were positive. A representative CD54+ cell line from each cancer was grown subcutaneously in SCID mice. Once the tumors were established. UV3 was administered using different dose regimens. UV3 slowed the growth of all 4 tumors, although it was not curative. When UV3 or gemcitabine were administered to SCID mice xenografted with a NSC lung tumor cell line or a pancreatic tumor cell line, UV3 was as effective as the chemotherapy alone. When gemcitabine and UV3 were administered together, the best anti-tumor responses were observed. UV3 has been chimerized (cUV3) and both toxicology studies and clinical trials are planned to assess the safety and activity of cUV3 in patients with one or more of these tumors. (C) 2008 Wiley-Liss. Inc.