Immunogenic FEAT protein circulates in the bloodstream of cancer patients

Abstract

[Background]FEAT is an intracellular protein that potently drives tumorigenesis in vivo. It is only weakly expressed in normal human tissues, including the testis. In contrast, FEAT is aberrantly upregulated in most human cancers. The present study was designed to investigate whether FEAT is applicable to tumor immunotherapy and whether FEAT is discernible in the bloodstream as a molecular biomarker of human cancers. [Methods]Two mouse FEAT peptides with predicted affinities for major histocompatibility complex H-2Kb and H-2Db were injected subcutaneously into C57BL/6 mice before subcutaneous transplantation of isogenic B16-F10 melanoma cells. Intracellular localization of FEAT was determined by immunogold electron microscopy. Immunoprecipitation was performed to determine whether FEAT was present in blood from cancer patients. A sandwich enzyme-linked immunosorbent assay was used to measure FEAT concentrations in plasma from 30 cancer patients and eight healthy volunteers. [Results]The vaccination experiments demonstrated that FEAT was immunogenic, and that immune responses against FEAT were induced without deleterious side effects in mice. Electron microscopy revealed localization of FEAT in the cytoplasm, mitochondria, and nucleus. Immunoprecipitation identified FEAT in the blood plasma from cancer patients, while FEAT was not detected in plasma exosomes. Plasma FEAT levels were significantly higher in the presence of cancers. [Conclusions]These findings suggest that FEAT is a candidate for applications in early diagnosis and prevention of some cancers.