Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases

Complications after vaccination, lack of vaccines against certain infections, and the emergence of antibiotic-resistant microorganisms point to the need for alternative ways of protection and treatment of infectious diseases. Here, we proposed a therapeutic approach to control salmonellosis based on...

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Veröffentlicht in:iScience 2020-12, Vol.23 (12), p.101854-101854, Article 101854
Hauptverfasser: Kalinina, Anastasiia A., Nesterenko, Ludmila N., Bruter, Alexandra V., Balunets, Denis V., Chudakov, Dmitriy M., Izraelson, Mark, Britanova, Olga V., Khromykh, Ludmila M., Kazansky, Dmitry B.
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Sprache:eng
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Zusammenfassung:Complications after vaccination, lack of vaccines against certain infections, and the emergence of antibiotic-resistant microorganisms point to the need for alternative ways of protection and treatment of infectious diseases. Here, we proposed a therapeutic approach to control salmonellosis based on adoptive cell therapy. We showed that the T cell receptor (TCR) repertoire of salmonella-specific memory cells contains 20% of TCR variants with the dominant-active α-chain. Transduction of intact T lymphocytes with the dominant salmonella-specific TCRα led to their enhanced in vitro proliferation in response to salmonella. Adoptive transfer of transduced T cells resulted in a significant decrease in bacterial loads in mice infected with salmonella before or after the adoptive transfer. We demonstrated that adoptive immunotherapy based on T cells, transduced with dominant-specific TCRα could be successfully applied for treatment and prevention of infectious diseases and represent a useful addition to vaccination and existing therapeutic strategies. [Display omitted] •A regular TCR repertoire of memory T cells contains alpha-chain-centric TCRs•Dominant-active TCRα, paired with random TCRβ, recognizes specific microbial antigens•Adoptive immunotherapy could be applied for treatment of infections Immunology; Microbiology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2020.101854