Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx
Introduction<p>T cell receptor-engineered T cell therapy has emerged as a promising approach in cancer immunotherapy, leveraging the ability of T cells to recognize tumor antigens presented on major histocompatibility complex molecules, offering a targeted approach for treating cancers. This s...
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| _version_ | 1849927635120947200 |
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| author | Saleh Alrhmoun (19193851) |
| author2 | Roman Perik-Zavodskii (19193839) Marina Fisher (19828437) Julia Lopatnikova (4164058) Olga Perik-Zavodskaia (19193842) Julia Shevchenko (19193845) Kirill Nazarov (19193854) Julia Philippova (19828440) Vasily Kurilin (19828443) Olga Kichakova (22680860) Evgenii Zavjalov (12230774) Elena Golikova (472121) Petr Timashev (10031740) Petr Glybochko (13011754) Sergey Sennikov (4164055) |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Saleh Alrhmoun (19193851) Roman Perik-Zavodskii (19193839) Marina Fisher (19828437) Julia Lopatnikova (4164058) Olga Perik-Zavodskaia (19193842) Julia Shevchenko (19193845) Kirill Nazarov (19193854) Julia Philippova (19828440) Vasily Kurilin (19828443) Olga Kichakova (22680860) Evgenii Zavjalov (12230774) Elena Golikova (472121) Petr Timashev (10031740) Petr Glybochko (13011754) Sergey Sennikov (4164055) |
| author_role | author |
| dc.creator.none.fl_str_mv | Saleh Alrhmoun (19193851) Roman Perik-Zavodskii (19193839) Marina Fisher (19828437) Julia Lopatnikova (4164058) Olga Perik-Zavodskaia (19193842) Julia Shevchenko (19193845) Kirill Nazarov (19193854) Julia Philippova (19828440) Vasily Kurilin (19828443) Olga Kichakova (22680860) Evgenii Zavjalov (12230774) Elena Golikova (472121) Petr Timashev (10031740) Petr Glybochko (13011754) Sergey Sennikov (4164055) |
| dc.date.none.fl_str_mv | 2025-11-25T10:46:20Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2025.1646404.s001 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Data_Sheet_1_Anti-HER2_neu_TCR-T_Cells_in_Action_linking_transcriptional_signatures_secretomics_and_In_Vivo_tumor_suppression_docx/30704999 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Genetic Immunology TCR-T cells TCR-T T cells adoptive cell therapy her2/neu ErbB2 ScRNA-seq |
| dc.title.none.fl_str_mv | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Introduction<p>T cell receptor-engineered T cell therapy has emerged as a promising approach in cancer immunotherapy, leveraging the ability of T cells to recognize tumor antigens presented on major histocompatibility complex molecules, offering a targeted approach for treating cancers. This study advances previous research conducted at the Laboratory of Molecular Immunology at RIFCI, where the full repertoire of HER2/neu-specific TCRs was identified. Specifically, here we are functionally validating a distinct TCR clonotype targeting the KIFGSLAFL peptide of HER2/neu protein presented by the HLA-A*02.</p>Methods<p>We employed an integrated approach combining in vitro cytotoxicity assays, single-cell RNA sequencing via BD Rhapsody, secretome profiling via LegendPlex, and in vivo HER2/neu-expressing xenograft models in SCID mice.</p>Results<p>Anti-HER2/neu TCR-T cells exhibited robust antigen-specific cytotoxicity in vitro, preferentially targeting tumor cells with high HER2/neu expression. Single-cell RNA sequencing revealed a unique double-positive (CD4+CD8+) T cell population emerging upon antigen engagement, characterized by a cytotoxic transcriptome with elevated granzyme B, granulysin, perforin, and TNF-α gene expression. Secretome profiling confirmed significantly enhanced production of effector molecules, including IL-2, granzyme B, TNF-α, and IFN-γ, supporting potent T cell activation and function. In vivo, anti-HER2/neu TCR-T cells achieved sustained and significant suppression of tumor growth in HER2/neu-expressing xenograft models, underscoring their therapeutic potential.</p>Discussion<p>These findings validate the broader utility of the previously identified HER2/neu-specific TCR repertoire and elucidate the molecular mechanisms driving its therapeutic efficacy, demonstrating the potential of TCR-T cells for treating solid tumors through robust cytotoxic activity and the emergence of a favorable CD4+CD8+ T cell population. This study offers critical mechanistic insights, establishing a foundation for advancing TCR-engineered therapies toward clinical use in HER2/neu-positive cancers.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_41fc30eb940e69a00c32ee30c05e4490 |
| identifier_str_mv | 10.3389/fimmu.2025.1646404.s001 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30704999 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docxSaleh Alrhmoun (19193851)Roman Perik-Zavodskii (19193839)Marina Fisher (19828437)Julia Lopatnikova (4164058)Olga Perik-Zavodskaia (19193842)Julia Shevchenko (19193845)Kirill Nazarov (19193854)Julia Philippova (19828440)Vasily Kurilin (19828443)Olga Kichakova (22680860)Evgenii Zavjalov (12230774)Elena Golikova (472121)Petr Timashev (10031740)Petr Glybochko (13011754)Sergey Sennikov (4164055)Genetic ImmunologyTCR-T cellsTCR-TT cellsadoptive cell therapyher2/neuErbB2ScRNA-seqIntroduction<p>T cell receptor-engineered T cell therapy has emerged as a promising approach in cancer immunotherapy, leveraging the ability of T cells to recognize tumor antigens presented on major histocompatibility complex molecules, offering a targeted approach for treating cancers. This study advances previous research conducted at the Laboratory of Molecular Immunology at RIFCI, where the full repertoire of HER2/neu-specific TCRs was identified. Specifically, here we are functionally validating a distinct TCR clonotype targeting the KIFGSLAFL peptide of HER2/neu protein presented by the HLA-A*02.</p>Methods<p>We employed an integrated approach combining in vitro cytotoxicity assays, single-cell RNA sequencing via BD Rhapsody, secretome profiling via LegendPlex, and in vivo HER2/neu-expressing xenograft models in SCID mice.</p>Results<p>Anti-HER2/neu TCR-T cells exhibited robust antigen-specific cytotoxicity in vitro, preferentially targeting tumor cells with high HER2/neu expression. Single-cell RNA sequencing revealed a unique double-positive (CD4+CD8+) T cell population emerging upon antigen engagement, characterized by a cytotoxic transcriptome with elevated granzyme B, granulysin, perforin, and TNF-α gene expression. Secretome profiling confirmed significantly enhanced production of effector molecules, including IL-2, granzyme B, TNF-α, and IFN-γ, supporting potent T cell activation and function. In vivo, anti-HER2/neu TCR-T cells achieved sustained and significant suppression of tumor growth in HER2/neu-expressing xenograft models, underscoring their therapeutic potential.</p>Discussion<p>These findings validate the broader utility of the previously identified HER2/neu-specific TCR repertoire and elucidate the molecular mechanisms driving its therapeutic efficacy, demonstrating the potential of TCR-T cells for treating solid tumors through robust cytotoxic activity and the emergence of a favorable CD4+CD8+ T cell population. This study offers critical mechanistic insights, establishing a foundation for advancing TCR-engineered therapies toward clinical use in HER2/neu-positive cancers.</p>2025-11-25T10:46:20ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fimmu.2025.1646404.s001https://figshare.com/articles/dataset/Data_Sheet_1_Anti-HER2_neu_TCR-T_Cells_in_Action_linking_transcriptional_signatures_secretomics_and_In_Vivo_tumor_suppression_docx/30704999CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307049992025-11-25T10:46:20Z |
| spellingShingle | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx Saleh Alrhmoun (19193851) Genetic Immunology TCR-T cells TCR-T T cells adoptive cell therapy her2/neu ErbB2 ScRNA-seq |
| status_str | publishedVersion |
| title | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| title_full | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| title_fullStr | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| title_full_unstemmed | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| title_short | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| title_sort | Data Sheet 1_Anti-HER2/neu TCR-T Cells in Action: linking transcriptional signatures, secretomics, and In Vivo tumor suppression.docx |
| topic | Genetic Immunology TCR-T cells TCR-T T cells adoptive cell therapy her2/neu ErbB2 ScRNA-seq |