Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies
Understanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration’s 2020 mandate. Using US HLA frequency data and census demographics we developed a method to create high-r...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/5/e011441.full |
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| author | Dirk Nagorsen Christian Roy Tomasz Sewastianik Ileana Saenz Gregory J Opiteck Sean Stagg Martin Maiers |
| author_facet | Dirk Nagorsen Christian Roy Tomasz Sewastianik Ileana Saenz Gregory J Opiteck Sean Stagg Martin Maiers |
| author_sort | Dirk Nagorsen |
| collection | DOAJ |
| description | Understanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration’s 2020 mandate. Using US HLA frequency data and census demographics we developed a method to create high-resolution HLA class 1 genotypic frequency maps. Analyzing HLA-A*11:01 and HLA-B*58:01 as alleles of interest, we found significant US regional variations. HLA-A*11:01, which presents KRAS neoantigen mutations targeted by TCR T-cell therapies, showed 10–15% genotypic frequency (national average 11.2%), with western US states 1.5 times higher than average and local variations within California (10–19%). These insights can be used to guide clinical trial site selection, for example, in National Cancer Institute (NCI) cancer center catchment areas. For HLA-B*58:01, which reacts pharmacogenetically with allopurinol and results in severe cutaneous adverse reactions, Mississippi had a high frequency among US states, which could be used to guide potential public safety campaigns. This method can identify regions with high HLA type representation, aiding efficient patient identification and enrollment for HLA-specific clinical trials and health-awareness efforts. |
| format | Article |
| id | doaj-art-ad879b09aeba47578ebc2094d9a25aba |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-ad879b09aeba47578ebc2094d9a25aba2025-08-20T02:58:18ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-05-0113510.1136/jitc-2024-011441Regional distribution of HLA frequencies in the USA: implications for TCR-based therapiesDirk Nagorsen0Christian Roy1Tomasz Sewastianik2Ileana Saenz3Gregory J Opiteck4Sean Stagg5Martin Maiers6Precision and Translational Medicine, Affini-T Therapeutics Inc, Watertown, Massachusetts, USAPrecision and Translational Medicine, Affini-T Therapeutics Inc, Watertown, Massachusetts, USAPrecision and Translational Medicine, Affini-T Therapeutics Inc, Watertown, Massachusetts, USAPrecision and Translational Medicine, Affini-T Therapeutics Inc, Watertown, Massachusetts, USAPrecision and Translational Medicine, Affini-T Therapeutics Inc, Watertown, Massachusetts, USANMDP, CIBMTR, Minneapolis, Minnesota, USANMDP, CIBMTR, Minneapolis, Minnesota, USAUnderstanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration’s 2020 mandate. Using US HLA frequency data and census demographics we developed a method to create high-resolution HLA class 1 genotypic frequency maps. Analyzing HLA-A*11:01 and HLA-B*58:01 as alleles of interest, we found significant US regional variations. HLA-A*11:01, which presents KRAS neoantigen mutations targeted by TCR T-cell therapies, showed 10–15% genotypic frequency (national average 11.2%), with western US states 1.5 times higher than average and local variations within California (10–19%). These insights can be used to guide clinical trial site selection, for example, in National Cancer Institute (NCI) cancer center catchment areas. For HLA-B*58:01, which reacts pharmacogenetically with allopurinol and results in severe cutaneous adverse reactions, Mississippi had a high frequency among US states, which could be used to guide potential public safety campaigns. This method can identify regions with high HLA type representation, aiding efficient patient identification and enrollment for HLA-specific clinical trials and health-awareness efforts.https://jitc.bmj.com/content/13/5/e011441.full |
| spellingShingle | Dirk Nagorsen Christian Roy Tomasz Sewastianik Ileana Saenz Gregory J Opiteck Sean Stagg Martin Maiers Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies Journal for ImmunoTherapy of Cancer |
| title | Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies |
| title_full | Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies |
| title_fullStr | Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies |
| title_full_unstemmed | Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies |
| title_short | Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies |
| title_sort | regional distribution of hla frequencies in the usa implications for tcr based therapies |
| url | https://jitc.bmj.com/content/13/5/e011441.full |
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