Autoantibodies as Biomarkers in Immuno-oncology

Cancer still accounts for nearly 1 in every 4 deaths worldwide. New immunotherapies have the power to induce durable responses in patients with fatal cancers, but only a small percentage of patients are responsive. Not only that but clinicians are also faced with new challenges with managing harmful immune-related adverse events (irAEs). A largely overlooked immune cell type in the context of immunotherapies are B cells, which can exert both anti-tumour and tumour-promoting effects by providing co-stimulatory signals and inhibitory signals for T cell activation, cytokines, and antibodies. B-cells produce anti-tumour antibodies, which can potentially mediate antibody-dependent cellular cytotoxicity (ADCC). It is well established that many cancer types induce an antibody response, which can even be used for early diagnostic purposes. Besides anti-tumour antigen (TAA) antibodies, cancer patients also produce autoantibodies that bind to self-antigens. Breakthrough of tolerance and elevated levels of autoantibodies is also a prominent feature of many autoimmune diseases. Hence, it is particularly relevant to investigate irAEs resembling autoimmune phenotypes.

In this presentation, we will discuss how autoantibody (AAB) profiling using the bead-based multiplex Luminex® Technology combined with machine-learning procedures offers a unique tool for biomarker research. Our SeroTag platform has been developed for quantifying the serum anti-tumour and auto-antibody reactivities towards customized and pre-validated panels of protein and peptide antigens (ImmunoINSIGHT by Oncimmune®). The highly dimensional data can be used to extract predictive models, identify biomarkers, create patient subgroups and also characterize regulatory networks involving cytokine and receptors suggesting that autoantibodies actively participate in immune regulation. Case studies for applications in melanoma CPI treatment and other cancers will be discussed.

Thus, autoantibodies hold the potential to serve as biomarkers of a sustained humoral anti-tumour response in cancer patients treated with immunotherapeutic approaches. Autoantibody measurements can be performed using easily accessible ‘liquid biopsy’ serum samples with minimal sample consumption and high stability. The deployment of an autoantibody immune assay can be easily achieved during clinical development using the identified reactive proteins and standard assay systems.

Learning Objectives:

1. Discuss autoantibodies and how they are relevant immunological biomarkers.

2. Explain how autoantibodies can also target cytokines, receptors they are involved in immune regulation.

3. Explain how autoantibody multiplexing and individual assays can be deployed during clinical research.