Abstract 1321: The use of proteomics to analyze whole tumors and identify unique immuno-oncology targets for antibody-based therapeutics
Authors: Ackroyd Jim , Bisht Arnima , Allen Jason , Hudson Lindsey , Barnes Martin , Rohlff Christian , Wilson Keith , Boyd Robert , Aud Dee 
Published: August 2015

The recent clinical success of the mAb therapeutics targeting immune checkpoint inhibitor proteins (PD-1/PD-L1, CTLA-4) has led to an increased appreciation of the potential of utilizing the immune system in oncology. There are two major strategies to elicit either a novel immune anti-tumor response or to reactivate a pre-existing anti-tumor response: by releasing a checkpoint inhibitory pathway via cell surface receptors (such as PD-1/PD-L1, CTLA-4) or by activation of co-stimulatory receptors (such as CD40, OX40, or GITR). Both of these strategies of immune modulation utilize cell surface receptors, and the targeting of antibody therapeutics with the appropriate functional activity to those receptors, to modify immune cell responses and allow for anti-tumor activity. The identification of novel immune-modulatory receptors with the potential to be immune-oncology therapeutic targets could be of high value to this anti-tumor approach.

OGAP is a unique proteomic database that integrates information at the tissue, disease and protein isoform level across diseases, indications, and normal tissues to clarify membrane protein expression levels and profiles. Specifically, it currently holds information on ∼16,000 human proteins sequenced, ∼7,000 membrane proteins, ∼35 tissues/organs, and ∼17 cancers. OGAP is fed by a proprietary sample preparation and processing workflow that relies on state-of-the-art high-throughput mass spectrometry and data processing to provide quantitative information on over 4,000 membrane-enriched proteins. OGAP has been used to identify novel oncology therapeutic targets for both ADC and BiTE-like approaches. Utilizing OGAP, membrane proteins present in tumors from five cancer indications (Pancreatic, Lung, Breast, Colorectal and Esophageal cancer) and multiple normal tissues or cells were analyzed. Validated immune cell markers (such as CD8, OX40, CD79B, TLR1, TLR2, TLR4, TLR7, CD56, CD204 and CD207) were profiled across different normal and tumor proteomic data sets. This analysis demonstrated we detect key immune cell markers in tumors and that different immune cell populations are found in tumors from the same or different cancer indications. The proteomic data sets were next analyzed for the presence of validated immuno-oncology targets (TIM3, PDL-1 and B7-H3). The expression patterns of these immune-oncology targets were analyzed to try and identify a unique protein signature. Using this protein expression profiling approach we identified most known immune-oncology targets, validating this as an approach to identify a pool of candidate novel immune-oncology targets. To further develop our approach we also used sequence based homology searching of uncharacterized membrane proteins to improve the quality of the pool of candidate novel immune-oncology targets. Several potential novel immune-oncology targets will be presented.

Citation Format: Jim Ackroyd, Arnima Bisht, Jason Allen, Lindsey Hudson, Martin Barnes, Christian Rohlff, Keith Wilson, Robert Boyd, Dee Aud. The use of proteomics to analyze whole tumors and identify unique immuno-oncology targets for antibody-based therapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1321. doi:10.1158/1538-7445.AM2015-1321