B cell differentiation and the production of tumour-specific antibodies are dynamic processes influenced by changing tumour antigen profiles and microenvironmental as well as systemic signals. Circulating antibody characteristics and dynamics can thus provide insight into bi-directional engagement between the immune system and the tumours. The ability to simultaneously assay a significant proportion of the systemic tumour antigen-specific antibody repertoire would thus provide a unique snapshot of the tumour at a given time point while circumventing the influence of inter- and intra-tumour heterogeneity that affects tissue-based techniques, thereby offering an attractive route to the discovery of novel blood-based biomarkers. Furthermore, unlike tumour antigens which are rapidly degraded upon entry into circulation, specific antibody titres are relatively stable.
We have developed a custom cancer microarray platform that can readily measure circulating antibodies against over 100 full-length correctly-folded cancer-specific and –associated antigens with high sensitivity. When screening healthy individuals on the array, no antibodies are detected, highlighting it’s specificity to cancer. In addition, the antigen content of the array is not restricted to a single cancer type. Thus, we aimed to investigate the translational uses of the array to detect novel diagnostic, prognostic and therapeutic monitoring biomarkers. To date, we have investigated the array’s use in melanoma, prostate cancer, breast cancer and colon cancer, yielding promising results.
Although the role of B cells in cancer is incompletely understood, the measurement of circulating tumour-specific antibodies represents a promising avenue in the search for cancer biomarkers.