Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

Kalinina, Anastasiia; Bruter, Alexandra V.; Nesterenko, L. N.; Хромых, Л. М.; Kazansky, Dmitry

doi:10.1016/j.xpro.2021.100368

Cited by 2 publications

(2 citation statements)

References 4 publications

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“…In our work, we employed Salmonella typhimurium as a model infection in mice to show that chain-centric TCRs are ordinarily generated during the immune response, and T cell clones with the dominant-active antigen-specific α-chain comprise a significant fraction (~20%) of the naturally forming pool of memory T cells [5,6]. We proved that antigenunchallenged T cells transduced with such dominant-active salmonella-specific TCRα could recognize bacterial antigens both in vitro and in vivo [5].…”

Section: Analysis Of the Immune Tcr Repertoirementioning

confidence: 99%

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T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

Kalinina,

Khromykh,

Kazansky

2023

IJMS

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T cells are crucial players in adaptive anti-cancer immunity. The gene modification of T cells with tumor antigen-specific T cell receptors (TCRs) was a milestone in personalized cancer immunotherapy. TCR is a heterodimer (either α/β or γ/δ) able to recognize a peptide antigen in a complex with self-MHC molecules. Although traditional concepts assume that an α- and β-chain contribute equally to antigen recognition, mounting data reveal that certain receptors possess chain centricity, i.e., one hemi-chain TCR dominates antigen recognition and dictates its specificity. Chain-centric TCRs are currently poorly understood in terms of their origin and the functional T cell subsets that express them. In addition, the ratio of α- and β-chain-centric TCRs, as well as the exact proportion of chain-centric TCRs in the native repertoire, is generally still unknown today. In this review, we provide a retrospective analysis of studies that evidence chain-centric TCRs, propose patterns of their generation, and discuss the potential applications of such receptors in T cell gene modification for adoptive cancer immunotherapy.

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Section: Analysis Of the Immune Tcr Repertoirementioning

confidence: 99%

“…Adoptive cell therapy (ACT) is a powerful strategy in the treatment of cancer and infectious diseases [1][2][3][4][5][6]. The gene modification of patients' T lymphocytes with tumor antigen-specific TCRs or chimeric antigen receptors (CARs) has become a milestone in the immunotherapy of hematological and solid malignancies.…”

Section: Introductionmentioning

confidence: 99%

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

Kalinina,

Khromykh,

Kazansky

2023

IJMS

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T-cell receptor chain centricity in the primarily activated effectors and re-stimulated memory cells

Kalinina,

Kubekina,

Persiyantseva

et al. 2024

BRSMU

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T cells, the adaptive immunity effectors, carry an antigen-recognizing T-cell receptor (TCR) that represents an αβ heterodimer. Functional dominance of one chain has been reported for a number of TCRs. This feature is called chain centricity. Today, it is unclear whether chain centricity is an inherent feature of some TCRs, and what mechanism underlies its development. The study aimed to determine the abundance of such receptors in the repertoire of primarily activated effectors and re-stimulated memory cells of mice specific to the allogeneic tumor antigens. The long-lived memory cells formed in the primary immune response in vivo were in vitro re-stimulated with the immunizing tumor cells. Primary effectors were obtained in vitro in the culture by stimulation of T cells of non-immunized mice with cells of the same allogeneic tumor. TCR libraries of effectors involved in the primary and secondary immune response were created by NGS sequencing. To identify chain-centric TCRs, 10 ТCRα variants were selected from each repertoire. T cells of intact mice were modified with individual TCR α-chain variants by transduction, with subsequent assessment of T cell proliferation under exposure to specific allogeneic stimulators. In vitro screening revealed 10% of chain-centric receptors in the primary effector pool, and the proportion of such TCRs in the repertoire of re-activated memory cells was 30%. Thus, chain centricity is an inherent property of some TCRs, but secondary antigenic stimulation can be a factor for selection of clonotypes with such receptors.

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Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

Cited by 2 publications

References 4 publications

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

T-cell receptor chain centricity in the primarily activated effectors and re-stimulated memory cells

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