Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer.

27 June 2024

A recent study conducted by Oncimmune, in collaboration with an oncologist from the Dana-Farber Cancer Institute in Boston, Massachusetts, and published in the Journal for ImmunoTherapy of Cancer, provided groundbreaking insights into the principal differences in autoantibody (AAb) profiles and clinical response between platinum-based chemotherapy (PBC) and immune checkpoint inhibitors (ICI) in metastatic urothelial cancer (mUC) patients.

The principal differences between chemotherapy and immune checkpoint inhibitors (ICIs) lie in their mechanisms of action: chemotherapy targets and kills rapidly dividing cancer cells directly, often affecting healthy cells as well, while ICIs work by blocking proteins that inhibit the immune response, thereby enabling the immune system to recognize and attack cancer cells more effectively.

In this collaborative study, autoantibodies were comprehensively profiled using Oncimmune’s SeroTag platform. One of the key findings was that patients treated with ICIs showed a greater induction of AAbs to self and tumour antigens compared to those receiving PBC. This increase in AAbs was associated with a better response to ICI therapy, indicating a more robust immune response activation with ICIs compared to PBC therapy.

The researchers also investigated AAbs in pre-treatment blood samples, which may have utility as biomarkers predicting clinical response and immune-related adverse events (irAEs). Specifically, AAbs against key tumour suppressor genes such as BRCA2, TP53, SPTBN1, FOXO1, and CTNNB1 were linked to a favourable response to therapy in mUC patients, indicating their potential as predictive biomarkers for treatment outcomes.

An important factor associated with better outcomes in patients undergoing ICI treatment is tumour mutational burden (TMB). Patients with TP53 mutations were more likely to have AAbs targeting the TP53 protein, which was linked to a positive response to therapy, suggesting a potential role of these AAbs as predictive biomarkers for treatment outcomes.

Additionally, specific AAbs against antigens like MITF, CDH3, and KDM4A were associated with the development of immune-related adverse events (irAEs) in patients receiving ICIs, indicating a potential role of these AAbs in predicting and monitoring treatment-related toxicities.

The study underscores the importance of comprehensive AAb profiling in understanding the humoral immune response in cancer and the differences seen in treatment strategies. These findings open up new avenues for personalized treatment strategies, potentially improving patient outcomes, and could pave the way for new diagnostic markers and therapeutic strategies in urothelial cancer. To delve deeper into the methodologies and detailed findings of this research, you can access the full paper here.