The Anti-Tumor Activity of UV3, an Anti-CD54 Antibody, in SCID Mice Xenografted with a Variety of Human Tumor Cell Lines
Brooks, Kimberly Joe
MetadataShow full item record
UV3, a monoclonal antibody that specifically recognizes human CD54, also known as intercellular adhesion molecule-1 (ICAM-1) was previously developed for the treatment of multiple myeloma. Even at low doses UV3 was highly effective at prolonging the survival of SCID mice with advanced multiple myeloma. Since CD54 is expressed on many different cancer types, we have now investigated the anti-tumor activity of UV3 in several other CD54+ tumors. A panel of 28 human non-Hodgkin's lymphoma, breast, prostate, non-small cell lung, pancreatic, and melanoma tumor cell lines was examined for reactivity with UV3, and 24 were strongly positive. A representative CD54+ cell line from each cancer type was then grown in SCID mice, and UV3 was administered using different dose regimens. UV3 prolonged survival and/or slowed tumor growth in all of the investigated tumor models, although it was not curative. When UV3 or gemcitabine were administered to SCID mice xenografted with non-small cell lung or pancreatic tumor cell lines, UV3 was as effective as the chemotherapy alone. However, the best anti-tumor responses were observed when gemcitabine and UV3 were administered together. In order to better understand how UV3 mediates its anti-tumor activity, some mechanisms of action were also investigated. Previous studies in multiple myeloma cells indicated that UV3 did not directly inhibit tumor cell growth or cell adhesion and that the Fc portion of UV3 was required for activity in mice. Similarly, in this study, UV3 did not induce cell cycle arrest or apoptosis in any of the tumor cell lines evaluated, and UV3 did mediate Fc effector mechanisms. However, the involvement of both Fc-dependent and Fc-independent mechanisms is suggested by the results, although the specific Fc-independent mechanisms are unknown. UV3 has already been chimerized (cUV3), and both toxicology studies and clinical trials are in the planning stage to assess the safety and activity of cUV3 in patients with one or more of these tumors.