FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2552613725> ?p ?o ?g. }

• W2552613725 abstract "Abstract Abstract 1902 Background and Purpose: Adult T-cell leukemia (ATL) is one of the most refractory forms of T-cell malignancy that preferentially affects aged population that constrains clinical efficacy of chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, objective responses in a small part of patients who received allo-HSCT evidently emphasize the therapeutic potential of immune-mediated approaches. While, some previous studies described that activation of human telomerase reverse transcriptase (hTERT), one of tumor antigens was detected in ATL tumor cells. Collectively, in this study, we examined the feasibility of redirected T-cell based immunotherapy targeting hTERT to explore a novel treatment strategy for ATL. Methods: Approval for this study was obtained from our institutional review board. Written informed consent was obtained from all patients, healthy volunteers, and parents of cord blood donors in accordance with the Declaration of Helsinki. HLA-A*2402-restricted and hTERT461–469 epitope (VYGFVRACL)-specific TCR-α/β genes were newly cloned into a novel retroviral vector encoding siRNAs for endogenous TCR-α/β genes (hTERT-siTCR vector). Using hTERT-siTCR vector, hTERT-siTCRR-α/β genes were transduced into normal peripheral CD8+ T cells (hTERT-siTCR/CD8+), employed as effectors. HLA-A*2402+ or HLA-A*2402− ATL cell lines, freshly isolated patients' ATL cells, normal peripheral blood mononuclear cells (PBMCs) from healthy volunteers, and CD34+ cells isolated from cord blood mononuclear cells (CBMCs) were employed as target cells. Anti-tumor reactivity mediated by hTERT-siTCR/CD8+ was assessed using standard 51Cr release assay. Expressions of hTERT mRNA and hTERT protein in ATL cell lines, freshly isolated ATL cells and normal CD4+ T cells were assessed by quantitative real-time PCR (QRT-PCR) and Western blotting. Frequencies of hTERT461–469–specific cytotoxic T-lymphocyte (CTL) precursors in periphery of ATL patients or healthy donors were measured by hTERT461–469/HLA-A*2402 tetramer assay. Finally, NOD/scid/γcnull (NOG) mice subcutaneously inoculated with luciferase-gene-modified HLA-A*2402+ ATL cell line, ATN-1 cells were treated with intravenous infusion of hTERT-siTCR/CD8+or non-gene-modified (NGM) ones, respectively. Thereafter, these mice were serially monitored for tumor growth using bioluminescence imaging and survival. Results: QRT-PCR and Western blotting revealed that hTERT was markedly overexpressed in both ATL cell lines and freshly isolated ATL cells, while less than undetectable in normal cells. hTERT461–469-specific CTL precursors were variably detectable in periphery of HLA-A*2402+ ATL patients, but not HLA-A*2402− ATL patients or HLA-A*2402+ healthy individuals. hTERT-siTCR/CD8+ were 30–50% positive for hTERT461–469/HLA-A*2402 tetramer and displayed HLA-A*2402-restricted and hTERT461–469–specific cytocidal activity against peptide-loaded K562-A24 cells. Those hTERT-siTCR/CD8+ successfully displayed tumoricidal activity against HLA-A*2402+ ATL cell line cells and freshly isolated HLA-A*2402+ ATL cells, but not HLA-A*2402− ones or HLA-A*2402+ normal cells including CD34+ CBMCs. Moreover, hTERT-siTCR/CD8+ generated from HLA-A*2402+ ATL patients also lysed autologous ATL tumor cells. Finally, using xenografted NOG mouse models, therapeutically infused hTERT-siTCR/CD8+, but not NGM ones from the identical donor successfully suppressed growth of inoculated ATL cells in vivo. Furthermore, NOG mice bearing advanced ATL tumor masses were also successfully treated with hTERT-siTCR/CD8+ in combination with bortezomib. Summary: In this study, we newly demonstrated that hTERT is a promising therapeutic tumor antigen for ATL. Moreover, redirected CD8+ T cells to express hTERT-specific TCR displayed antitumor activity against ATL tumor cells both in vitro and in vivo. Furthermore, our preliminary data represented antitumor activity against advanced ATL, in combination with bortezomib. Collectively, redirected T cell-based immunotherapy targeting hTERT seems clinically feasible and promising for the treatment of almost all ATL patients who are ineligible for allo-HSCT. Disclosures: No relevant conflicts of interest to declare." @default.
• W2552613725 created "2016-11-30" @default.
• W2552613725 creator A5006439326 @default.
• W2552613725 creator A5020638934 @default.
• W2552613725 creator A5034547906 @default.
• W2552613725 creator A5038817476 @default.
• W2552613725 creator A5040085191 @default.
• W2552613725 creator A5052778790 @default.
• W2552613725 creator A5053119596 @default.
• W2552613725 creator A5060157655 @default.
• W2552613725 creator A5061841627 @default.
• W2552613725 creator A5069618140 @default.
• W2552613725 date "2012-11-16" @default.
• W2552613725 modified "2023-09-27" @default.
• W2552613725 title "Human Telomerase Reverse Transcriptase–specific T-Cell Receptor Gene Transfer Redirects T Cells to Display an Effective Antitumor Reactivity Against Adult T-Cell Leukemia" @default.
• W2552613725 doi "https://doi.org/10.1182/blood.v120.21.1902.1902" @default.
• W2552613725 hasPublicationYear "2012" @default.
• W2552613725 type Work @default.
• W2552613725 sameAs 2552613725 @default.
• W2552613725 citedByCount "0" @default.
• W2552613725 crossrefType "journal-article" @default.
• W2552613725 hasAuthorship W2552613725A5006439326 @default.
• W2552613725 hasAuthorship W2552613725A5020638934 @default.
• W2552613725 hasAuthorship W2552613725A5034547906 @default.
• W2552613725 hasAuthorship W2552613725A5038817476 @default.
• W2552613725 hasAuthorship W2552613725A5040085191 @default.
• W2552613725 hasAuthorship W2552613725A5052778790 @default.
• W2552613725 hasAuthorship W2552613725A5053119596 @default.
• W2552613725 hasAuthorship W2552613725A5060157655 @default.
• W2552613725 hasAuthorship W2552613725A5061841627 @default.
• W2552613725 hasAuthorship W2552613725A5069618140 @default.
• W2552613725 hasConcept C104317684 @default.
• W2552613725 hasConcept C125593758 @default.
• W2552613725 hasConcept C137061746 @default.
• W2552613725 hasConcept C147483822 @default.
• W2552613725 hasConcept C154317977 @default.
• W2552613725 hasConcept C159047783 @default.
• W2552613725 hasConcept C167672396 @default.
• W2552613725 hasConcept C195616568 @default.
• W2552613725 hasConcept C202751555 @default.
• W2552613725 hasConcept C203014093 @default.
• W2552613725 hasConcept C2776090121 @default.
• W2552613725 hasConcept C2780914630 @default.
• W2552613725 hasConcept C2908647359 @default.
• W2552613725 hasConcept C502942594 @default.
• W2552613725 hasConcept C55493867 @default.
• W2552613725 hasConcept C71924100 @default.
• W2552613725 hasConcept C86803240 @default.
• W2552613725 hasConcept C8891405 @default.
• W2552613725 hasConcept C94581717 @default.
• W2552613725 hasConcept C99454951 @default.
• W2552613725 hasConceptScore W2552613725C104317684 @default.
• W2552613725 hasConceptScore W2552613725C125593758 @default.
• W2552613725 hasConceptScore W2552613725C137061746 @default.
• W2552613725 hasConceptScore W2552613725C147483822 @default.
• W2552613725 hasConceptScore W2552613725C154317977 @default.
• W2552613725 hasConceptScore W2552613725C159047783 @default.
• W2552613725 hasConceptScore W2552613725C167672396 @default.
• W2552613725 hasConceptScore W2552613725C195616568 @default.
• W2552613725 hasConceptScore W2552613725C202751555 @default.
• W2552613725 hasConceptScore W2552613725C203014093 @default.
• W2552613725 hasConceptScore W2552613725C2776090121 @default.
• W2552613725 hasConceptScore W2552613725C2780914630 @default.
• W2552613725 hasConceptScore W2552613725C2908647359 @default.
• W2552613725 hasConceptScore W2552613725C502942594 @default.
• W2552613725 hasConceptScore W2552613725C55493867 @default.
• W2552613725 hasConceptScore W2552613725C71924100 @default.
• W2552613725 hasConceptScore W2552613725C86803240 @default.
• W2552613725 hasConceptScore W2552613725C8891405 @default.
• W2552613725 hasConceptScore W2552613725C94581717 @default.
• W2552613725 hasConceptScore W2552613725C99454951 @default.
• W2552613725 hasLocation W25526137251 @default.
• W2552613725 hasOpenAccess W2552613725 @default.
• W2552613725 hasPrimaryLocation W25526137251 @default.
• W2552613725 hasRelatedWork W1489950790 @default.
• W2552613725 hasRelatedWork W1522592546 @default.
• W2552613725 hasRelatedWork W1564959198 @default.
• W2552613725 hasRelatedWork W1589230527 @default.
• W2552613725 hasRelatedWork W1982440887 @default.
• W2552613725 hasRelatedWork W1984390981 @default.
• W2552613725 hasRelatedWork W2008463303 @default.
• W2552613725 hasRelatedWork W2019802173 @default.
• W2552613725 hasRelatedWork W2023107901 @default.
• W2552613725 hasRelatedWork W2074101304 @default.
• W2552613725 hasRelatedWork W2096564238 @default.
• W2552613725 hasRelatedWork W2126312346 @default.
• W2552613725 hasRelatedWork W2127169662 @default.
• W2552613725 hasRelatedWork W2407818500 @default.
• W2552613725 hasRelatedWork W2415543209 @default.
• W2552613725 hasRelatedWork W2465991532 @default.
• W2552613725 hasRelatedWork W2556167380 @default.
• W2552613725 hasRelatedWork W2589019585 @default.
• W2552613725 hasRelatedWork W2890466817 @default.
• W2552613725 hasRelatedWork W2979997083 @default.
• W2552613725 isParatext "false" @default.
• W2552613725 isRetracted "false" @default.
• W2552613725 magId "2552613725" @default.
• W2552613725 workType "article" @default.