scholarly journals The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction

2020 ◽  
Vol 21 (14) ◽  
pp. 5013
Author(s):  
Tabito Kino ◽  
Mohsin Khan ◽  
Sadia Mohsin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
T Cell ◽  
Inflammatory Response ◽  
Stem Cell Transplantation ◽  
Immune Cells ◽  
Tissue Repair ◽  
Ischemic Injury ◽  
T Cell Subsets

Ischemic injury to the heart causes cardiomyocyte and supportive tissue death that result in adverse remodeling and formation of scar tissue at the site of injury. The dying cardiac tissue secretes a variety of cytokines and chemokines that trigger an inflammatory response and elicit the recruitment and activation of cardiac immune cells to the injury site. Cell-based therapies for cardiac repair have enhanced cardiac function in the injured myocardium, but the mechanisms remain debatable. In this review, we will focus on the interactions between the adoptively transferred stem cells and the post-ischemic environment, including the active components of the immune/inflammatory response that can mediate cardiac outcome after ischemic injury. In particular, we highlight how the adaptive immune cell response can mediate tissue repair following cardiac injury. Several cell-based studies have reported an increase in pro-reparative T cell subsets after stem cell transplantation. Paracrine factors secreted by stem cells polarize T cell subsets partially by exogenous ubiquitination, which can induce differentiation of T cell subset to promote tissue repair after myocardial infarction (MI). However, the mechanism behind the polarization of different subset after stem cell transplantation remains poorly understood. In this review, we will summarize the current status of immune cells within the heart post-MI with an emphasis on T cell mediated reparative response after ischemic injury.

Abstract 13: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yanqing Gong ◽  
Jane Hoover-Plow ◽  
Ying Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tissue Repair ◽  
Critical Role ◽  
Cardiac Repair ◽  
Internal Diameter ◽  
Hematopoietic Stem

Ischemic heart disease, including myocardial infarction (MI), is the primary cause of death throughout the US. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms regulating G-CSF-induced cardiac repair may offer novel approaches for strengthening stem cell-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated cardiac repair after MI. Our data show that G-CSF significantly improves cardiac tissue repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue repair and heart function by G-CSF is observed in Plg -/- mice, indicating that Plg is required for G-CSF-regulated cardiac repair after MI. To investigate whether Plg regulates HPSC recruitment to ischemia area, bone marrow transplantion (BMT) with EGFP-expressing BM cells was performed to visualize BM-derived stem cells in infarcted tissue. Our data show that G-CSF dramatically increases recruitment of GFP+ cells (by 16 fold) in WT mice but not in Plg -/- mice, suggesting that Plg is essential for HPSC recruitment from BM to the lesion sites after MI. In further studies, we investigated the role of Plg in the regulation of SDF-1/CXCR-4 axis, a major regulator for HPSC recruitment. Our results show that G-CSF significantly increases CXCR-4 expression in infarcted area in WT mice. While G-CSF-induced CXCR-4 expression is markedly decreased (80%) in Plg -/- mice, suggesting Plg may regulate CXCR-4 expression during HSPC recruitment to injured heart. Interestingly, Plg does not affect SDF-1 expression in response to G-CSF treatment. Taken together, our findings have identified a critical role of Plg in HSPC recruitment to the lesion site and subsequent tissue repair after MI. Thus, targeting Plg may offer a new therapeutic strategy to improve G-CSF-mediated cardiac repair after MI.

scholarly journals Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

2020 ◽  
Vol 21 (19) ◽  
pp. 7301 ◽  
Author(s):  
Kamila Raziyeva ◽  
Aiganym Smagulova ◽  
Yevgeniy Kim ◽  
Saltanat Smagul ◽  
Ayan Nurkesh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Heart Function ◽  
Cellular Reprogramming ◽  
Genetic Manipulations ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.

In Chronic Myeloid Leukemia Cytotoxic T Cell Responses to BMI-1 Protein Correlate with Higher Expression of BMI-1 in Leukemia Progenitors, and May Contribute to Improved Outcome After Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 192-192
Author(s):  
S. M. Agnes Yong ◽  
Nicole Stephens ◽  
Bipin N. Savani ◽  
Yixin Li ◽  
Rhoda Eniafe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
Immune Responses ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Cell Responses ◽  
Specific Ctls

Abstract Abstract 192 The polycomb group (PcG) proteins BMI-1 and EZH2 are key regulators of self-renewal processes in normal and leukemic stem cells. Of these two PcG proteins, BMI-1 is more highly expressed in chronic myeloid leukemia (CML) than in normal stem cells, and is associated with a more rapid disease progression in patients who are treated with drug therapy alone, implying that an increased level of “stem-ness” conferred by BMI-1 contributes to leukemogenicity. Conversely, CML patients with high BMI-1 expression prior to allogeneic stem cell transplantation (SCT) have better overall survival post-transplant (Mohty, et al, Blood 2008). To investigate the potential of PcG proteins as leukemia-associated antigens, and targets for graft-versus-leukemia (GVL) effects, we studied a cohort of 86 CML patients (54 chronic phase, 32 advanced phase) who received T-cell depleted SCT with T-cell add-back on day 45-100 post-SCT from HLA-identical sibling donors. Using quantitative real-time PCR, we measured the expression of EZH2, BMI-1 and its target for repression, CDKN2A (encoding p16INK4A) in CD34+ progenitors and their CD34-negative counterparts. Using flowcytometric detection of intracellular cytokines IFN-γ or TNF-α, and degranulation marker CD107a, in CD8+ cytotoxic T lymphocytes (CTL), we assessed immune responses to BMI-1 (TLQDIVYKL and CLPSPSTPV) and EZH2 (YMCSFLFNL and SQADALKYV) peptides in 25 HLA-A*0201+ patient-donor pairs. Seven of 17 (41%) HLA-A*0201+ CML patients had native immune responses to BMI-1 peptide, which was associated with higher BMI-1 expression in CD34+ progenitors (p=0.04, Mann-Whitney U test). Five of 25 (20%) healthy HLA-A*0201+ sibling donors had detectable immune responses to BMI-1 peptide. EZH2 was less immunogenic compared to BMI-1 in both patients and donors. The majority of peptide-specific CTLs analyzed by peptide-specific dextramers had central memory phenotype. BMI-1- or EZH2-specific T cells were readily detected after 7-day cultures using an ELISPOT assay in 75% of donors or patients where peptide-specific CTLs were detected ex-vivo. A higher expression of BMI-1 in CML patients pre-SCT and correspondingly lower expression of its target for repression, CDKN2A, was associated with improved leukemia-free survival (p=0.01), and reduced disease-related death (p=0.0001). In four HLA-A*0201+ patients whose donors had immune responses to PcG peptides, BMI-1 or EZH2-specific T cell responses were detected in the first 120 days post-SCT. CML patients who had donors with immune responses to BMI-1 peptide had improved leukemia-free survival compared to patients whose donors were non-responders (80% vs. 60% respectively). Immune responses to PcG proteins, in particular to BMI-1, may be relevant for disease control by GVL effects. Unlike CTLs specific for primary granular proteins such as proteinase 3 and elastase, which are also highly expressed in CML cells, CTLs against BMI-1 and EZH2 may be less susceptible to selective deletion processes resulting in tolerance, as these proteins are less ubiquitously expressed by mature progenitors which are expanded in CML, and are therefore good GVL and immunotherapy target candidates in CML. Furthermore, these CTLs have the potential to target leukemia stem cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Regulatory Effect of Mesenchymal Stem Cells on T Cell Phenotypes in Autoimmune Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Zhiping Wei ◽  
Jintao Yuan ◽  
Gaoying Wang ◽  
Dickson Kofi Wiredu Ocansey ◽  
Zhiwei Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Tissue Repair ◽  
T Cell Subsets ◽  
Autoimmune Conditions ◽  
T Cell Phenotypes ◽  
Cell Phenotypes

Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.

scholarly journals PEMANFAATAN SEL PUNCA PADA INFARK MIOKARD

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Loretta C. Wangko ◽  
J. H. Awaloei ◽  
Janry A. Pangemanan
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Tissue Repair ◽  
Heart Function ◽  
Improve Heart Function ◽  
Β Blockers ◽  
Causes Of Deaths ◽  
Myocardial Thickness

Abstract: World-wide, myocardial infarction and heart failure are still the leading causes of deaths and use up a great deal of money. In myocardial infarction there frequently incur cardiomyocyte injuries. Naturally, resident cardiomyocytes will undergo proliferation and contribute to the increasing and repairing of myocardium post infarction. Unfortunately, this capacity of regeneration is very limited. Moreover, injured cardiomyocytes are replaced by scar tissues. Pharmacotherapy with ACE-Inhibitors and β blockers can give some clinical improvement, but can not inhibit the loss of cardiomyocytes. Nowadays, stem cell therapy has proclaimed some promising benefits. Among all the introduced stem cells, mesenchymal stem cells are the most popular since they have the capability to differentiate and then to develop into cardiomyocytes, maintain the myocardial thickness, reduce heart remodeling of the non infarct myocardium, improve heart function, and can be used from allogenic donors. Besides that, these cells are easier to obtain and isolate, are genetically stable, have the capacity for angiogenesis, homing to the injured areas or inflammation, and supplying growth factors and cytokines for tissue repair. Key words: stem cell, cardiomyocyte, transplantation, donor.     Abstrak: Infark miokard dan gagal jantung masih merupakan penyebab kematian utama di dunia dan menyerap biaya pengobatan yang tinggi. Pada infark miokard sering terjadi cedera kardiomiosit. Secara alamiah kardiomiosit residen akan mengalami proliferasi dan mengambil bagian dalam meningkatkan dan memulihkan miokard pasca infark. Kapasitas regenerasi ini sangat terbatas. Selain itu kardiomiosit yang cedera akan digantikan oleh jaringan ikat. Farmakoterapi dengan penghambat ACE dan β bloker dapat memberikan perbaikan klinis, tetapi tidak dapat menghambat kehilangan kardiomiosit. Dewasa ini terapi sel punca telah mengumandangkan manfaat yang menjanjikan. Dari berbagai sel punca yang dikemukakan, sel punca mesensimal yang paling diminati oleh karena kemampuannya berdiferensiasi dan berkembang menjadi kardiomiosit, mempertahankan ketebalan miokard, menurunkan remodeling jantung pada bagian yang tidak infark, memperbaiki fungsi jantung. dan dapat diambil dari donor alogenik. Disamping itu, sel-sel ini lebih mudah diperoleh dan diisolasi, stabil secara genetik, berkapasitas angiogenesis, homing ke tempat cedera atau inflamasi, dan memasok growth factors dan sitokin untuk perbaikan jaringan. Kata kunci: sel punca, kardiomiosit, transplantasi, donor.

scholarly journals Alterations of Peripheral Blood T Cell Subsets following Donor Lymphocyte Infusion in Patients after Allogeneic Stem Cell Transplantation

Hemato ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 692-702
Author(s):  
Ann-Kristin Schmaelter ◽  
Johanna Waidhauser ◽  
Dina Kaiser ◽  
Tatjana Lenskaja ◽  
Stefanie Gruetzner ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Donor Lymphocyte Infusion ◽  
T Cell Subsets ◽  
Mixed Chimerism

Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) is an established method to enhance the Graft-versus-Leukemia (GvL) effect. However, alterations of cellular subsets in the peripheral blood of DLI recipients have not been studied. We investigated the changes in lymphocyte subpopulations in 16 patients receiving DLI after successful alloSCT. Up to three DLIs were applied in escalating doses, prophylactically for relapse prevention in high-risk disease (n = 5), preemptively for mixed chimerism and/or a molecular relapse/persistence (n = 8), or as part of treatment for hematological relapse (n = 3). We used immunophenotyping to measure the absolute numbers of CD4+, CD8+, NK, and CD56+ T cells and their respective subsets in patients’ peripheral blood one day before DLI (d-1) and compared the results at day + 1 and + 7 post DLI to the values before DLI. After the administration of 1 × 106 CD3+ cells/kg body weight, we observed an overall increase in the CD8+ and CD56+ T cell counts. We determined significant changes between day − 1 compared to day + 1 and day + 7 in memory and activated CD8+ subsets and CD56+ T cells. Applying a higher dose of DLI (5 × 106 CD3+ cells/kg) led to a significant increase in the overall counts and subsets of CD8+, CD4+, and NK cells. In conclusion, serial immune phenotyping in the peripheral blood of DLI recipients revealed significant changes in immune effector cells, in particular for various CD8+ T cell subtypes, indicating proliferation and differentiation.

scholarly journals Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naïve T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201

2014 ◽  
Vol 32 (22) ◽  
pp. 2365-2372 ◽  
Author(s):  
Edmund K. Waller ◽  
Brent R. Logan ◽  
Wayne A.C. Harris ◽  
Steven M. Devine ◽  
David L. Porter ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Cells ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Purpose To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor–mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Patients and Methods Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Results Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8+ T cells (CD8Tns), or naïve CD4+ T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Conclusion Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation.

scholarly journals Advancement in Stem Cell Therapy for Ischemic Myocardial Cell: A Systematic Review

2018 ◽  
Author(s):  
Syeda Beenish Bareeqa ◽  
Fazeela Bibi ◽  
Syed Ijlal Ahmed ◽  
Syeda Sana Samar
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Human Subjects ◽  
Physiological State ◽  
Medical Application ◽  
Cell Renewal ◽  
Hematopoietic Stem

Background: Cardiac muscle possesses a limited capacity to regenerate its tissue on its own. It is less likely to reverse the altered cardiac functioning to its normal physiological state after a major myocardial infarction. Stem cell transplantation provided a unique therapeutic approach in managing such injuries. There has been a substantial debate about the complexity, scope and medical application of stem cell transplantation in past few years. Materials and Methods: An extensive review of medical literature was conducted to establish the consensus about the possible mechanism of cell renewal, associated complications and risks of failure of this technique. Twenty cases of mammalian animals and twenty-four cases of stem cell transplantation in human subjects were reviewed. Results: Most common associated complication was re-stenosis of coronary artery. Few clinical trials reported the failure in improving cardiac functioning. The success rate of stem cell transplantation was remarkable in the literature related to experimental animal subjects. Conclusion: It was concluded that renewal of the cardiac cell is a result of induction of angiogenesis and prolonged cell survival. This topic still requires an immense amount of research to fill the gap in adequate knowledge.   Keywords: Mesenchymal stem cells, Myocardial infarction, Cardiomyocytes, Hematopoietic stem cells

Development of Novel Stem Cell Transplantation and Gene-Immunotherapy Using WT1-Specific T-Cell Receptor Gene.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3028-3028
Author(s):  
Toshiki Ochi ◽  
Hiroshi Fujiwara ◽  
Kozo Nagai ◽  
Toshiaki Shirakata ◽  
Kiyotaka Kuzushima ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem Cells ◽  
Cell Transplantation ◽  
Clinical Efficacy ◽  
Cd8 T Cells ◽  
Hematopoietic Stem

Abstract Abstract 3028 Poster Board II-1004 Purpose The Wilms' tumor 1 (WT1) is one of the zinc-finger transcriptional regulators, and its expression level is very low in most tissues of adults. In contrast, various kinds of leukemia and solid tumors express WT1 abundantly, and high expression level of WT1 is correlated with disease aggressiveness and poor prognosis. These findings indicate that WT1 is a promising target antigen for anti-cancer cellular immunotherapy. Following identification of immunogenic epitopes derived from WT1 which are recognized by HLA class I-restricted and HLA class II-restricted T cells, phase I/II WT1 peptide vaccination trials have been conducted. Although the positive correlation between the clinical efficacy and vaccine-induced WT1-specific T-cell response has been reported, the clinical efficacy is not satisfactory. Adoptive transfer of WT1-specific T cells seems to be the promising approach to achieve marked improvement in clinical efficacy of WT1-targeting immunotherapy, however, it still remains difficult to expand WT1-specific T cells sufficiently ex vivo. To overcome these problems, we attempted to establish gene-immunotherapy targeting WT1 using T-cell receptor (TCR) gene isolated from the WT1-specific T-cell clone. We also verified the feasibility of novel stem cell transplantation by transducing WT1-specific TCR gene into hematopoietic stem cells. Methods We cloned the full length TCR-αa and -β genes from a WT1235-243-specific and HLA-A*2402-restricted cytotoxic T lymphocyte (CTL) clone. The WT1-specific TCR gene-repressing retroviral and lentiviral vectors were constructed. Retroviral vector was transduced to human peripheral T cells in retronectin-coated plate. WT1-specific functions of TCR gene-transduced CD8+ T cells and CD4+ T cells were examined by evaluating WT1 peptide-specific cytotoxicity by 51Cr-release assay and WT1 peptide-specific Th1 cytokine production, respectively. To improve the efficacy of WT1-specific TCR expression, we developed the novel retroviral vector which can inhibit selectively intrinsic TCR expression (si-TCR vector). Finally, we transduced the WT1-specific TCR lentiviral vector into human cord blood CD34+ cells, and transplanted them to NOD/SCID/common-γnull mice. Then, we examined whether WT1-specific human mature T cells can differentiate in mice. The presence of WT1-specific human T cells in mice was determined by tetramer assay and IFN-γ production in response to stimulation with WT1 peptide. Results Following transfer of WT1-specific TCR gene into peripheral blood lymphocytes, WT1 peptide-specific CD8+ and CD4+ T cells could be expanded easily in vitro. TCR gene-transduced CD8+ T cells exerted cytotoxicity against WT1 peptide-pulsed target cells and human leukemia cells in an HLA-A*2402-restricted manner. Similarly, TCR gene-transduced CD4+ T cells showed WT1-specific Th1 cytokine production in response to stimulation with human leukemia cells in HLA-A*2402-restricted fashion depending on the interaction of CD4 and HLA class II molecules. The newly developed si-TCR vector appeared to inhibit expression of endogenous TCR efficiently and improved the efficacy of WT1-specific TCR expression 3 to 5-fold higher as compared to the conventional vector. Three months after transplantation of WT1-specific TCR gene-transduced human hematopoietic stem cells in NOD/SCID/common-γnull mice, differentiation of WT1-specific human T cells in murine spleen was evaluated. Tetramer assay revealed that human mature T cells expressing WT1-specific TCR on their cell surface were clearly detected. Furthermore, these WT1-specific CD8+ T cells appeared to produce IFN-γ in response to stimulation with WT1 peptide-loaded HLA-A*2402-positive cells. Conclusion The adoptive gene-immunotherpay using WT1-specific TCR gene against leukemia seems to be promising. Moreover, the novel stem cell transplantation using WT1-specific TCR gene-transduced hematopoietic stem cells might open the door to induce long-lasting anti-leukemic cellular immunity in patients with leukemia. Disclosures No relevant conflicts of interest to declare.

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