ADAMANT · ANTIBODY DERIVATIVES AS MOLECULAR AGENTS FOR NEOPLASTIC TARGETING

The selective delivery of bioactive agents (cytotoxics, radionuclides, cytokines) at the tumor site, while sparing normal tissues, represents one of the most promising avenues for the development of anticancer therapies with unprecedented efficacy and tolerability. Monoclonal antibodies represent the preferred vehicle for the targeted delivery of bioactive agents to cancer sites, as they can display a preferential accumulation in primary and metastatic tumor lesions already few hours after intravenous administration. Certain monoclonal antibody derivatives can remain on the neoplastic mass for several days, thus enabling the slow release of potent cytotoxics or the continuous action of bioactive agents such as cytokines or therapeutic radionuclides. The ADAMANT Project aims at the generation of anticancer agents of superior quality, which rely on the antibody-based delivery of cytotoxics, radionuclides or immunostimulatory cytokines to either vascular tumor antigens or to tumor cell membranes. While clinically-validated antibodies will allow the rapid development of therapeutic strategies based on novel antibody derivatives, innovative perfusion-based chemical proteomic technologies will facilitate the discovery of accessible and abundant tumor-associated antigens, ideally suited for the targeted delivery of bioactive agents to cancer sites. Imaging methodologies will guide us in the selection of antigens, antibodies and therapeutic agents with optimal pharmacokinetis and pharmacodynamics. Finally, therapy studies in tumor-bearing mice, featuring the use of antibody-derivatives in combination with other anti-cancer drugs (cytotoxic, biological, vascular disrupting agents) will provide insights about how to best translate the results of the ADAMANT Project to clinical development. The Project will be truly successful if at least one antibody-based tumor targeting agent enters full-blown industrial development programs by the end of the ADAMANT Project.