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PRAME and HLA Class I expression patterns make synovial sarcoma a suitable target for PRAME specific T-cell receptor gene therapy. | LitMetric

AI Article Synopsis

  • - The study explores the potential of PRAME-TCR gene therapy as a treatment for synovial sarcoma, focusing on how PRAME-specific T-cells can identify and attack sarcoma cells
  • - Researchers found that PRAME is consistently expressed in all tested synovial sarcoma samples, while the expression of HLA class I (HLA-I) is generally low but increases in certain tumor areas, especially in biphasic synovial sarcoma cases
  • - The results suggest that the combination of high PRAME expression and elevated HLA-I in specific tumor regions may make synovial sarcoma a viable candidate for targeted PRAME-specific TCR-gene therapy

Article Abstract

Synovial sarcoma expresses multiple cancer testis antigens that could potentially be targeted by T-cell receptor (TCR) gene therapy. In this study we investigated whether PRAME-TCR-gene therapy could be an effective treatment for synovial sarcoma by investigating the potential of PRAME-specific T-cells to recognize sarcoma cells and by evaluating the expression patterns of and HLA class I (HLA-I) in synovial sarcoma tumor samples. All expressing sarcoma cell lines, including 2 primary synovial sarcoma cell cultures (passage < 3), were efficiently recognized by PRAME-specific T-cells. mRNA FISH demonstrated that was expressed in all synovial sarcoma samples, mostly in an homogeneous pattern. Immunohistochemistry demonstrated low HLA-I baseline expression in synovial sarcoma, but its expression was elevated in specific areas of the tumors, especially in biphasic components of biphasic synovial sarcoma. In 5/11 biphasic synovial sarcoma patients and in 1/17 monophasic synovial sarcoma patients, elevated HLA-I on tumor cells was correlated with infiltration of T-cells in these specific areas. In conclusion, low-baseline expression of HLA-I in synovial sarcoma is elevated in biphasic areas and in areas with densely infiltrating T-cells, which, in combination with homogeneous and high expression, makes synovial sarcoma potentially a suitable candidate for PRAME-specific TCR-gene therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279314PMC
http://dx.doi.org/10.1080/2162402X.2018.1507600DOI Listing

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