Background Recent FDA-approved checkpoint inhibitors targeting the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1)/PD-L1 pathway represent milestones in the field of cancer immunotherapy. In general, cancer immunotherapy works only in a subset of patients, but some patients experience prolonged responses. Cancer immunotherapy can cause severe immune-related adverse events (irAE) in patients, who are increasingly seen by rheumatologists. We propose that that autoantibody profiling will reveal novel B-cell associated mechanisms of therapy response and side effects. This may yield minimally-invasive biomarkers to identify patients at risk to develop iRAE and monitor cancer patients over the course of their life under immunotherapy
Objectives We have developed a novel Cancer Immunotherapy Array, which includes a combination of antigens important in autoimmune diseases, anti-tumour immunity, and oncogenes and tested the array in patient sera from a diverse set of cancer immunotherapy trials.
Methods The Cancer Immunotherapy Array consists of a bead-based multiplex array using minimal patient serum samples incubated with antigen-coated, color-coded Luminex beads. Run in microtiter plate format, the Array permits quantification of the autoantibody reactivity in thousands of serum samples towards approximately 900 human protein antigens in each sample. Magnetic beads are employed to enable automated pipetting and washing steps.1 We selected human protein antigens from groups A) tumor-associated antigens (TAA), B) autoimmune disease antigens, C) cytokines, and D) cancer signalling pathway proteins
Results In total, over 2000 serum samples from diverse cancer indications plus hundreds of samples from autoimmune diseases such as RA, SLE, Sjogren’s disease and healthy controls were screened with the Cancer Immunotherapy Array. As key findings we report autoantibody panels which can differentiate patients with irAEs and those without irAEs. Also, but less prominent, individual autoantibodies are associated with overall survival. Autoantibodies that target antigens involved in cancer signalling pathways are associated with irAEs. Also, patients with increased levels of a distinct autoantibody against an inflammatory cytokine do not develop irAEs across multiple tumours.
Conclusions The Cancer Immunotherapy Array is a high throughput array suitable for the analysis of thousands of cancer patient serum samples. Its first application presents novel autoantibody signatures for therapy-related toxicities (irAEs) as well as response. These signatures have the potential to serve as useful tools that will broaden our understanding of the mechanisms of therapy response and irAE occurrence.
Reference  Budde P, et al. Lupus. 2016;25:812–22.
Disclosure of Interest P. Schulz-Knappe Shareholder of: Protagen AG, P. Budde Employee of: Protagen AG, H.-D. Zucht Employee of: Protagen AG, S. Konings Employee of: Protagen AG, L. Steeg Employee of: Protagen AG, E. Friedrich Employee of: Protagen AG, C. Gutjahr Employee of: Protagen AG, R. Steil Employee of: Protagen AG, S. Bhandari Employee of: Protagen AG, M. Tuschen Employee of: Protagen AG
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