High Throughput Membrane Proteomics For The Discovery Of Oncology Targets Ideally Suited For The Development Of Antibody Drug Conjugates (Adcs)

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Antibody Drug Conjugates (ADCs) are showing tremendous promise for cancer patients as recently demonstrated by the dramatic responses reported in breast cancer and Hodgkin's Lymphoma clinical trials to the ADCs T-DM1 and SGN-35. We have developed proteomics methods to enrich for membrane proteins that are expressed preferentially in cancer cells over normal cells. Potential ADC targetable proteins are then validated using the proprietary OGAP database as well as conventional expression analysis tools. The proteomics processes have identified novel cancer specific proteins as well as cancer specific isoforms of known proteins. These targets are then combined with large panels of antibodies to discover potential therapeutics with properties desirable for the development of ADCs. Antibodies are selected which : a) preferentially bind to tumor cells over normal cells, b) have good specificity and affinity, c) show high prevalence in target cancer indications by IHC, d) internalize on antigen binding, e) bind to relevant tox species tissues as they bind to human tissues. Here we describe the proteomics processes and use of the OGAP database and demonstrate the development of candidate therapeutic antibodies with the potential to become ADCs, which are directed to novel targets and cancer specific isoforms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1683. doi:10.1158/1538-7445.AM2011-1683