NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma

Abstract

Background: Novel immune therapies targeting tumor specific antigens are being developed. Our purpose was to determine expression of the cancer testes antigen NY-ESO-1 in renal cell carcinoma (RCC), as NY-ESO-1 targeting approaches, particularly adoptive cell therapy, have not been evaluated in this disease.Methods: We employed tissue microarrays containing >300 unique RCC cases and adjacent benign renal tissue to determine NY-ESO-1 expression using a quantitative immunofluorescence method. In addition, we studied NY-ESO-1 expression in 35 matched primary and metastatic RCC specimens to assess concordance between different tumor sites.Results: NY-ESO-1 was highly expressed in a subset of RCCs. Expression in primary RCC specimens was significantly higher than adjacent normal renal tissue (P<0.0001) and higher in clear cell carcinomas than papillary RCC (P<0.0001). Expression levels in metastatic specimens were higher than in matched primary samples (P=0.0018), and the correlation between the two sites was modest (χ2=3.5, p=0.06).Conclusions: Aberrant NY-ESO-1 expression seen in clear cell RCC suggests that NY-ESO-1 targeting approaches should be studied in this disease. Expression is higher in metastatic sites, and discordance between primary and metastatic sites in some patients suggests that patient selection for these therapies should be based on expression in metastatic rather than nephrectomy specimens.

Application of Serex-Analysis for Identification of Human Colon Cancer Antigens

“…KY-CC-19/TSGA2 mRNA expression also increased at 7 times in tumor case N3 and at 10 times in tumor case N9, despite for colon cancer cases NN 1, 2, 4, 5, 8 its normal expression down regulated at 2-3.5 times (Figure, b). KY-CC-15/PLRG1 mRNA in addition to tumor case N7 have slightly increased expression at 3 times in tumor case N3 and near the same level of expression compare to normal colon in tumor cases NN 1,2,4,5,6,8,9 (difference range at 0.48-1.96) (Figure, c). KY-CC-15/PLRG1 and KY-CC-19/TSGA2 represent the genes with selective activation of normal expression in some cases of colon cancer and may be immunogenic as aberrantly expressed.…”

“…overexpressed or with activity in tumor cells (activated only in neoplastic cells and silence in normal cells, overexpressed in tumor cells, mutated genes), those can predict its possible association with tumorigenesis [6]. Several tumor-specific antigens such as NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins are promising sensitive and specific target molecules for cancer screening and diagnosis, cancer immuno-therapy and development of antigen-specific cancer vaccines [7][8][9].…”

Development of experimental mouse xenograft models of human tumors for preclinical in vivo studies of product for cellular immunotherapy

“…NY-ESO-1 -это опухоль-ассоциированный белок, который ограниченно экспрессируется в нормальных тканях, но резко повышает уровень экспрессии в эпителиальных опухолях яичников и других солидных новообразованиях. Функция NY-ESO-1 до сих пор неизвестна, но предполагается, что он может участвовать в иммортализации, самообновлении, миграции [12]. Раково-тестикулярный антиген MAGE-A4 имеет высокий уровень экспрессии в метастазах солидных опухолей по сравнению с первичными опухолями, но отсутствует в большинстве нормальных тканей [13].…”

Renal Cell Carcinoma: A Cancer-testis Antigen Poor Malignancy

“…Elevated expression levels of NY-ESO-1 have been demonstrated in a proportion of RCC samples in another study with higher expressions observed in metastatic samples compared with the corresponding primary tumors. NY-ESO-1 expression has been considerably higher in primary RCC samples compared with adjacent normal renal tissues and in clear cell carcinomas compared with papillary RCC [17].…”