Poster Presentation 31st Lorne Cancer Conference 2019

Diagnosis and disease evolution during immunotherapy - longitudinal profiling of autoantibodies using high-content protein arrays (#313)

Chris Schmidt 1 , Yong Sheng 1 , Catherine Lanagan 1 , Huang Wang 1 , Antonia Pritchard 2 , Victoria Atkinson 3 , Gregor S Kijanka 1
  1. Mater Research Institute - The University on Queensland, Woolloongabba, QLD, Australia
  2. UHI Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
  3. Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia

Patients with cancer have antibodies against tumour antigens. The autoantibody repertoires in patients may reflect aberrant molecular and cellular processes during tumorigenesis, ultimately revealing novel diagnostic or therapeutic biomarkers. We use a high-content protein array approach that allows us to detect and characterise antigen-specific antibodies in sera of cancer patients against up to 10k human proteins. Personalised antibody profiles in patients with colorectal cancer, melanoma and normal controls show a wide range of antigen-specific antibodies against several hundred to several thousand self-proteins. This distribution is not disease-specific and remains stable in each donor over years in the absence of pathological changes. 

With the onset of tumour growth neoplastic changes emerge and novel, tumour specific antibodies are induced. Those antibodies can be readily identified using protein arrays and utilised for diagnostic purposes across multiple immunoglobulin isoforms [1-3]. The corresponding antigens are often aberrantly expressed in tumour tissue and reveal prognostic biomarker properties [4, 5]. The protein array platform is therefore especially adept to investigate antibody repertoire changes in cancer patients undergoing immunotherapy. Since IgG antibodies require linked antigen recognition by cognate B and CD4+ T cells, antibody profiles provide a novel method to investigate a critical arm of anti-tumour immunity. We present novel findings from a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine showing antigen-specific antibodies in patients with durable complete clinical responses, partial responses and progressive disease. We link those further to CD8+ peptidome and predicted neoantigen data and compare our findings to novel antibody profiles in advanced melanoma patients undergoing checkpoint inhibitor immunotherapy.

In summary, we demonstrate that profiling serum antibodies in cancer patients provides an excellent opportunity to develop novel diagnostic and predictive biomarkers. The characterisation of tumour specific antigens can furthermore elucidate immune-related mechanisms in cancer immunotherapy.

  1. 1. Fitzgerald, S., et al., Measurement of the IgM and IgG Autoantibody Immune Responses in Human Serum has High Predictive Value for the Presence of Colorectal Cancer. Clin Colorectal Cancer, 2018. Sept 27. doi: 10.1016/j.clcc.2018.09.009
  2. 2. O'Reilly, J.A., et al., Diagnostic potential of zinc finger protein-specific autoantibodies and associated linear B-cell epitopes in colorectal cancer. PLoS One, 2015. 10(4): p. e0123469.
  3. 3. Kijanka, G., et al., Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer. Gut, 2010. 59(1): p. 69-78.
  4. 4. Fitzgerald, S., et al., Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment. J Transl Med, 2018. 16(1): p. 89
  5. 5. Fitzgerald, S., et al., High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer. J Pathol Clin Res, 2015. 1(1): p. 54-65.