Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies

Background:Immunotherapies, including cancer vaccines and immune checkpoint inhibitors have transformed the management of many cancers. However, a large number of patients show resistance to these immunotherapies and current research has provided limited findings for predicting response to precision immunotherapy treatments.Methods:Here, we applied the next generation phage display mimotope variation analysis (MVA) to profile antibody response and dissect the role of humoral immunity in targeted cancer therapies, namely anti-tumor dendritic cell vaccine (MelCancerVac(& REG;)) and immunotherapy with anti-PD-1 monoclonal antibodies (pembrolizumab).Results:Analysis of the antibody immune response led to the characterization of epitopes that were linked to melanoma-associated and cancer-testis antigens (CTA) whose antibody response was induced upon MelCancerVac & REG; treatments of lung cancer. Several of these epitopes aligned to antigens with strong immune response in patients with unresectable metastatic melanoma receiving anti-PD-1 therapy.Conclusions:This study provides insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments. The antibody epitopes as biomarkers reflect melanoma-associated features of immune response, and also provide insights into the molecular pathways contributing to the pathogenesis of cancer. Concluding, antibody epitope response can be useful in predicting anti-cancer immunity elicited by immunotherapy. Plain language summaryImmunotherapy treatments, which utilize the patient's own immune system to fight cancer, have become a standard treatment of cancer. However, for many patients' immunotherapy does not work. During the immune response the body produces proteins called antibodies. This study characterized the antibodies produced following treatment with two different types of immunotherapies that treat skin cancer, to gain insights into how the immune system responds in different individuals. Our results demonstrate that multiple proteins that are present in patients with skin cancer are specifically targeted by the immune system during skin cancer specific immunotherapy. Our results should help further anti-cancer drug development. Rahni et al profile antibody response in patients with varied response to cancer immunotherapies. They identify antibody epitope responses that predict anti-cancer immunity elicited by immunotherapy.

Automated summary

This study used phage display mimotope variation analysis to profile antibody response in cancer patients receiving immunotherapy. The findings provide insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments, and suggest that antibody epitopes can be used as biomarkers to predict anti-cancer immunity elicited by immunotherapy.