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REVIEW: Analysis of the Repertoires of Circulating Autoantibodies’ Specificities as a Tool for Identification of the Tumor-Associated Antigens: Current Problems and Solutions

Pavel V. Belousov1,2

1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

2National Center for Personalized Medicine of Endocrine Diseases, National Medical Research Center of Endocrinology, Ministry of Health of the Russian Federation, 117036 Moscow, Russia

Received July 27, 2020; Revised August 17, 2020; Accepted August 24, 2020
Circulating autoantibodies against tumor-associated autoantigens (TAA) may serve as valuable biomarkers for a wide range of diagnostic purposes. Modern immunology offers a large variety of methods for in-depth comparative analysis of the repertoires of circulating antibodies’ antigenic specificities in health and disease. Nevertheless, this research field so far has met somewhat limited clinical success, while numerous data on the repertoires of circulating autoantibodies’ specificities in cancer patients are poorly integrated into the contemporary picture of the immunological and molecular landscapes of human tumors. This review is an attempt to identify and systematize the key and essentially universal conceptual and methodological limitations of analyses of the repertoires of circulating antibodies’ antigenic specificities in cancer (expression bias, redundancy of TAA repertoires, identification of natural IgG, the absence of the pathogenetically relevant context in the experimental systems used to detect TAA), as well as to discuss potential and already known methodological improvements that may significantly increase the detectability of the pathogenetically relevant and diagnostically significant bona fide TAA.
KEY WORDS: tumor-associated antigens, autoantibodies, cancer biomarkers, immunoproteomics

DOI: 10.1134/S0006297921100060