HLA-A, B, C and DR locus specificities studied in 168 patients (71 Chronic active Hepatitis, 97 Chronic Persistent Hepatitis) serologically and histopathologically proven Chronic Hepatitis B Virus infection. There were 113 men and 55 women with a mean age of 23.2 (21-52) years. Hundred and seventy four healthy subjects (107 men, 67 women) included in control group with a mean age of 26.4 (20-54) years. The frequency of HLA A3 (p < 0.01), HLA A11 (p < 0.01), HLA B35 (p < 0.05) and HLA B51 (p < 0.01) were significantly higher in patients than in healthy control subjects. Comparisons among the other HLA-A, B, C and DR locus were found to be statistically non-significant.
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Cancer Immunol Res
January 2025
Vanderbilt University, Nashville, TN, United States.
Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Swiss Institute of Bioinformatics, Lausanne, Switzerland
Background: The adoptive cell transfer (ACT) of T cell receptor (TCR)-engineered T cells targeting the HLA-A2-restricted epitope NY-ESO-1 (A2/NY) has yielded important clinical responses against several cancers. A variety of approaches are being taken to augment tumor control by ACT including TCR affinity-optimization and T-cell coengineering strategies to address the suppressive tumor microenvironment (TME). Most TCRs of clinical interest are evaluated in immunocompromised mice to enable human T-cell engraftment and do not recapitulate the dynamic interplay that occurs with endogenous immunity in a treated patient.
View Article and Find Full Text PDFIdentification of eight novel HLA-A alleles by next-generation sequencing.
View Article and Find Full Text PDFFront Immunol
January 2025
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.
View Article and Find Full Text PDFT cell receptor (TCR) mimics offer a promising platform for tumor-specific targeting of peptide-MHC in cancer immunotherapy. Here, we designed a α-helical TCR mimic (TCRm) specific for the NY-ESO-1 peptide presented by HLA-A 02, achieving high on-target specificity with nanomolar affinity (K = 9.5 nM).
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