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At least 19 recordsLinked to original sources
PubMed2025

Comparative HLA Alleles and Haplotypes of Bone Marrow Volunteers Recruiting in the Asian and European Parts of Russia.

HLA typing of 9126 haematopoietic stem cell donors living in the Asian and European parts of Russia and identifying themselves as Russians was performed using NGS technology in 2-field resolution at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The study of donors in the Asian part of Russia disclosed 77 alleles at the HLA-A locus, 111 at the HLA-B locus, 58 at the HLA-C locus, 54 at the HLA-DRB1 locus, and 26 at the HLA-DQB1 locus. Donors of the European part of Russia are characterised by the following allelic diversity: 87 alleles at the HLA-A locus, 136 at the HLA-B locus, 72 at the HLA-C locus, 67 at the HLA-DRB1 locus, and 37 at the HLA-DQB1 locus. The most common five-locus haplotype in both populations is HLA-A*01:01 ~ HLA-C*07:01 ~ HLA-B*08:01 ~ HLA-DRB1*03:01 ~ HLA-DQB1*02:01. Throughout the study, 26 new alleles were revealed.

Humans↗
PubMed2026

Receptor-defined targeting of a genomically unique melanoma-enriched noncanonical antigen.

Effective T cell-based immunotherapies require functional receptors that can be engineered and redeployed to recognize tumor-restricted antigens. Noncanonical peptides arising from transcription outside annotated protein-coding regions expand the antigenic landscape of cancer; however, systematic strategies to biologically prioritize and functionally validate such targets remain underdeveloped. Here, we integrated de novo transcript analysis, exon-resolved quantification, RNA in situ hybridization, and immunopeptidomics to identify melanoma-associated noncanonical transcripts and advance candidates through receptor-level validation. Among three recurrent melanoma-associated transcripts, EVA003 emerged as a lead target based on its distinct repeat-enriched genomic architecture, consistent tumor-enriched exon-level expression across independent datasets, and a genomically unique immunogenic core sequence. We demonstrate endogenous presentation of EVA003-derived peptides on HLA-A*03:01 and detect specific reactivity in patient-derived tumor-infiltrating lymphocytes. Single-cell transcriptomic profiling identified a dominant peptide-reactive clonotype, enabling isolation of a naturally occurring T cell receptor. Transfer of this receptor into healthy donor T cells conferred antigen-dependent activation and cytotoxicity against both peptide-pulsed targets and melanoma cells expressing EVA003 endogenously. Together, these findings establish a biologically informed strategy for prioritizing noncanonical tumor antigens and demonstrate that genomically unique, tumor-enriched noncanonical peptides can be presented to molecularly defined receptors capable of mediating cancer cell killing. These findings support the integration of prioritized noncanonical antigens into engineered T cell therapeutic strategies.

Humans↗
PubMed2026

Mass Spectrometry-Based Profiling of Personalized Immunopeptidomes in Thai Renal Cell Carcinoma.

This study profiles the personalized immunopeptidomes of 13 Thai patients with renal cell carcinoma (RCC), addressing a critical knowledge gap in Southeast Asian populations characterized by distinct HLA allele distributions. We combined whole-exome sequencing (WES)-based personalized proteome construction with liquid chromatography-tandem mass spectrometry (LC-MS/MS), using both database-driven searches and de novo peptide sequencing. HLA typing identified several class I allotypes that are underrepresented in publicly available immunopeptidome resources, including seven alleles not previously represented in the databases examined; HLA-A*11:01 was the most frequent allele in this cohort. Database-based analysis identified a single tumor-specific neoantigen derived from a mutant JADE2 peptide in the patient with the highest tumor mutational burden, which was validated by a mutant-specific ELISPOT response. In contrast, de novo sequencing revealed numerous noncanonical peptides, a subset of which were supported by proteogenomic validation using PepQuery and detected exclusively in cancer proteomes but not in normal tissue data sets, indicating their potential as tumor-associated antigen candidates. Together, these results establish an integrated and scalable framework for identifying HLA-presented tumor-derived peptides and provide a foundational immunopeptidome resource to support personalized cancer immunotherapy development in Southeast Asia.

Humans↗