Over the past decade, anticancer therapies have shifted from empiric cytotoxic compounds that exhibit a broad ability to inhibit cell growth to more rationally designed target-based therapies.1 The goal of this approach is to develop increasingly selective anticancer therapies that avoid the traditional side effects of cytotoxic chemotherapy. Toward this end, antibody-based therapies are becoming increasingly utilized to recognize and direct this type of specific antitumor strategy. Early efforts in this area were often disappointing and hampered by ineffective antibody-mediated

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cell killing effects, difficulty in achieving tumor specificity, toxicity of the monoclonal antibody (mAb), and immunogenicity of the murine mAb. Moreover, the effectiveness of mAbs as mono-therapy in solid tumors, as compared to lymphoid malignancies, has generally been much more limited despite the ability to target specific tumor antigens.2,3 Reasons for these failures have included the observation that many tumor antigens are not unique to tumors but are shared by normal tissues, leading to increased toxicity in those organs that express the targeted antigen. In addition, the ability of large monoclonal antibodies to navigate into a tumor bed may be inhibited by poor vascularization and increased internal pressure of the tumor relative to the surrounding tissue.4 Improvements in the design of mAbs have, however, been steady and have included the use of smaller less immunogenic fragments and linkage to a variety of agents.2,5 SGN-15, a novel immunoconjugate linking the monoclonal antibody BR96, which targets tumors expressing a LewisY (LeY)-related antigen and the chemotherapeutic agent doxorubicin represent examples of this approach. Furthermore, the observation that antitumor activity is improved through the combination of conventional chemotherapeutic agents with monoclonal antibodies has suggested a unique strategy to target specific tumors and improve existing therapies.