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Advances in preclinical TCR characterization: leveraging cell avidity to identify functional TCRs.
Carr, Andreas; Mateyka, Laura M; Scheu, Sebastian J C; Bici, Ana; Paijmans, Joris; Reijmers, Rogier M; Dieminger, Nina; Dildebekova, Shirin; Hamed, Noomen; Wagner, Karolin; Busch, Dirk H; D'Ippolito, Elvira.
Afiliação
  • Carr A; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Mateyka LM; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Scheu SJC; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Bici A; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Paijmans J; LUMICKS, Paalbergweg 3, NL-1105 AG, Amsterdam, The Netherlands.
  • Reijmers RM; LUMICKS, Paalbergweg 3, NL-1105 AG, Amsterdam, The Netherlands.
  • Dieminger N; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Dildebekova S; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Hamed N; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Wagner K; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
  • Busch DH; CellPoint, a Galapagos Company, Oegstgeest, The Netherlands.
  • D'Ippolito E; 9184 Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine and Health, Technical University of Munich , Munich, Germany.
Biol Chem ; 405(7-8): 517-529, 2024 Jul 26.
Article em En | MEDLINE | ID: mdl-38666334
ABSTRACT
T-cell therapy has emerged as an effective approach for treating viral infections and cancers. However, a significant challenge is the selection of T-cell receptors (TCRs) that exhibit the desired functionality. Conventionally in vitro techniques, such as peptide sensitivity measurements and cytotoxicity assays, provide valuable insights into TCR potency but are labor-intensive. In contrast, measuring ligand binding properties (z-Movi technology) could provide an accelerated processing while showing robust correlations with T-cell functions. In this study, we assessed whether cell avidity can predict functionality also in the context of TCR-engineered T cells. To this end, we developed a flexible system for TCR re-expression by generating a Jurkat-derived T cell clone lacking TCR and CD3 expression through CRISPR-Cas9-mediated TRBC knockout. The knockin of a transgenic TCR into the TRAC locus restored TCR/CD3 expression, allowing for CD3-based purification of TCR-engineered T cells. Subsequently, we characterized these engineered cell lines by functional readouts, and assessment of binding properties through the z-Movi technology. Our findings revealed a strong correlation between the cell avidities and functional sensitivities of Jurkat TCR-T cells. Altogether, by integrating cell avidity measurements with our versatile T cell engineering platform, we established an accelerated system for enhancing the in vitro selection of clinically relevant TCRs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T Limite: Humans Idioma: En Revista: Biol Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T Limite: Humans Idioma: En Revista: Biol Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha