TY - JOUR

T1 - TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors

AU - Alsalloum, Alaa

AU - Alrhmoun, Saleh

AU - Shevchenko, Julia

AU - Fisher, Marina

AU - Philippova, Julia

AU - Perik-Zavodskii, Roman

AU - Perik-Zavodskaia, Olga

AU - Lopatnikova, Julia

AU - Kurilin, Vasily

AU - Volynets, Marina

AU - Akahori, Yasushi

AU - Shiku, Hiroshi

AU - Silkov, Alexander

AU - Sennikov, Sergey

N1 - This work was carried out with the support of the Russian Science Foundation, project number 21-65-00004 (https://rscf.ru/en/project/21-65-00004/, accessed on 20 April 2021).

PY - 2023/10/16

Y1 - 2023/10/16

N2 - Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer.

AB - Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85175485012&origin=inward&txGid=f1a7146cbe49f80badd471195c73075a

U2 - 10.3390/biomedicines11102805

DO - 10.3390/biomedicines11102805

M3 - Article

C2 - 37893178

VL - 11

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 10

M1 - 2805

ER -