Abstract

An Overview on the Characterisation of Antibody Specificities and Off Target Activities of Antibodies

Dolores Cahill, Professor, University College Dublin

The successful development of monoclonal antibodies (mAbs) for cancer therapy involves a complex process of scientific and preclinical evaluations, including the detailed specificity analysis of the antigen expression and the analysis of the specificity and cross-reactivity of the monoclonal antibody to this antigen, such as using high content protein array technology. Also the study of the immune effector functions and signalling pathway effects of the antibody is required and the analysis of in vivo antibody localization and the analysis of the in vivo therapeutic activity of the antibody. Antibody-drug conjugates combine the mAb and small molecule drugs, (or radioisotopes, or toxins) to selectively kill targeted cells while minimizing toxicity to normal cells. The development of antibody-drug conjugates (and therapeutic antibodies) in cancer treatment requires in depth understanding of the specificity of the antibody, the antibody-drug conjugate, cancer serology, protein expression and protein-engineering techniques, mechanisms of action and disease progression, disease resistance and the interplay between the immune system and cancer cells. This presentation will give an overview of the methods for the characterisation of the specificities of the antibody alone, antibody-drug conjugates specificities and off target activities. This talk will also give an overview of the advantages of knowing this information and will include examples from academia, pre-clinical and clinical studies.