Antibody-Based Therapeutics for Cancer

Weiner, Louis

Abstract

Monoclonal antibodies have emerged as increasingly important therapeutic vehicles for the treatment of cancer and other human diseases. Selected unconjugated antibodies can exert clinically meaningful anti-tumor effects in important cancers such as breast cancer and lymphomas. The mechanisms underlying these exciting results remain to be elucidated, but most likely include the induction of host immune responses and the perturbation of signaling through growth factor receptors. Antibody conjugates have been used to deliver toxic principles such as radioactive particles, chemotherapy agents and catalytic toxins with increasing success in defined clinical settings. Advances in antibody engineering have permitted the systematic evaluation of structural manipulation on targeting and efficacy. Antibodies with novel specificities can be isolated with increasing ease from naive and immunized phage display libraries. Major challenges in this rapidly evolving field include the development of improved means for identifying new targets, including structurally-defined (e.g., through proteomic or genomic screening) and functionally-defined approaches. New approaches are needed to harness the ability of antibodies to initiate and sustain innate and adaptive immune responses. For immunoconjugate strategies to consistently succeed without undue host toxicity, new strategies must be developed to dissociate the process of antibody distribution from the effects of antibody-directed tumor targeting. This meeting will address these challenges in distinct sessions devoted to antibody structure and function, immunoconjugates, antibodies as tools for target discovery, antibodies as signaling agents and immune effectors, and in a session that highlights clinical advances in the field. Leaders in each of these areas will present their work and discussion periods will be used to highlight areas felt to have particular promise.