REVIEW: Immunogenicity of Fluorescent Tumor Models Based on Colored Fluorescent Proteins, Ways for Overcoming It and Using It

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Nadezhda K. Marynich¹, Alexandra V. Gavshina¹, Milana M. Verdish^1,2, Alexander P. Savitsky¹, and Irina G. Meerovich^1,a*

¹Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences, 119071 Moscow, Russia

²Yeltsin Ural Federal University, 620002 Ekaterinburg, Russia

^* To whom correspondence should be addressed.

Received: July 15, 2025; Revised: September 25, 2025; Accepted: October 20, 2025

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Fluorescent proteins (FP) are widely used to visualize biological processes in living cells, including their use as genetically encoded markers for molecular and cellular research. However, their expression, even at the cellular level, could lead to some difficulties in interpreting molecular events due to protein–cell interactions. At the level of immunocompetent organisms, immune mechanisms could also take place, complicating the work with the cells expressing fluorescent proteins and interpretation of the experimental results. This led to the study of immunogenicity of FPs in the models of various diseases, in particular, cancer, and development of the models exhibiting immune tolerance to FP. This review describes various approaches for selecting disease models that are more immunotolerant to the expression of fluorescent proteins, and for reducing immunogenicity of both FP-expressing tumor models and some other diseases models. It highlights the ways to use the increased immunogenicity of the fluorescent tumors in experimental oncology, as well highlights some aspects of reducing immunogenicity of the fluorescent proteins exogenously administered to laboratory animals.

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KEY WORDS: fluorescent proteins, tumor models, immunocompetent animals, immunogenicity, epitope

DOI: 10.1134/S0006297925603922

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