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

Rähni, Annika; Jaago, Mariliis; Sadam, Helle; Pupina, Nadežda; Pihlak, Arno; Tuvikene, Jürgen; Annuk, Margus; Mägi, Andrus; Timmusk, Tõnis; Ghaemmaghami, Amir M.; Palm, Kaia

Abstract

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®) 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® 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.

Citation

Rähni, A., Jaago, M., Sadam, H., Pupina, N., Pihlak, A., Tuvikene, J., …Palm, K. (2022). Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies. Communications Medicine, 2(1), Article 48. https://doi.org/10.1038/s43856-022-00114-7

• Journal Article Type: Article
• Acceptance Date: Apr 25, 2022
• Online Publication Date: May 11, 2022
• Publication Date: 2022-12
• Deposit Date: May 12, 2022
• Publicly Available Date: May 12, 2022
• Journal: Communications Medicine
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 1
• Article Number: 48
• DOI: https://doi.org/10.1038/s43856-022-00114-7
• Public URL: https://nottingham-repository.worktribe.com/output/8046462
• Publisher URL: https://www.nature.com/articles/s43856-022-00114-7
• Additional Information: Received: 20 July 2021; Accepted: 25 April 2022; First Online: 11 May 2022; : A.P. and K.P. are inventors of the patent application (PCT Application No. US/14079626) filed by Protobios that covers the use of phage display method for manipulating and monitoring humoral immunity. All other authors declare no competing interests.