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1.
Medicina (B.Aires) ; 81(3): 337-345, jun. 2021. graf
Article in Spanish | LILACS | ID: biblio-1346468

ABSTRACT

Resumen Las leucemias agudas constituyen la neoplasia más frecuente en pacientes pediátricos. Actualmente, el 80% de los niños con leucemia linfoblástica aguda (LLA) logran curarse con quimioterapia con vencional pero el 20% de los mismos presentarán una reaparición de la enfermedad. La enfermedad residual medible (ERM) ha sido descripta como un importante factor pronóstico, que permite evaluar la respuesta de los pacientes al tratamiento. Una de las técnicas más sensibles par a estudiar ERM es la cuantificación de reordena mientos génicos de inmunoglobulinas (Ig) y receptores de linfocitos-T (TCR). Los objetivos del presente trabajo fueron describir los reordenamientos detectados de Ig/TCR, evaluar el efecto de la ERM en la supervivencia de niños con LLA y comparar la ERM por Ig/TCR con la cuantificada mediante citometría de flujo multiparamétrica (CFM). Del total de 455 pacientes estudiados, en el 96% fue posible caracterizar al menos un reordenamiento de Ig/TCR. El total de reordenamientos clonales detectados fue de 1550. La ERM pudo ser estudiada en forma exitosa en el 89% de los casos. El valor de ERM positiva combinada al día 33 y 78 de tratamiento, permitió identificar pacientes de alto riesgo, entre los previamente estratificados por la ERM mediante CFM al día 15. La comparación entre la determinación de ERM mediante reordenamientos Ig/TCR y CFM mostró una excelente correlación. El presente trabajo constituye un estudio de ERM mediante Ig/TCR realizado en un número muy significativo de pacientes diagnosticados en forma consecutiva, tratados en el marco de un protocolo homogéneo y con excelente seguimiento clínico.


Abstract Acute leukemias are the most common neoplasm in pediatric patients. Currently, 80% of children with diagnosis of acute lymphoblastic leukemia (ALL) are cured with conventional chemotherapy, but 20% of them will have a recurrence of the disease. Measurable Residual Disease (MRD) has been described as an important prognostic factor that allows evaluating the response of patients to treatment. One of the most sensitive techniques to study MRD is the quantification of immunoglobulins (Ig) and T-lymphocyte receptors (TCR) genes rearrangements. The aims of this study were to describe the detected Ig/TCR rearrangements, to evaluate the prognostic impact of MRD in our population of children with ALL and to compare the MRD values by Ig/TCR with those obtained by multiparametric flow cytometry (MFC). A total of 455 patients were studied. In 96% of the cases, it was possible to characterize at least one Ig/TCR rearrangement. The total number of Ig/TCR rear rangements detected was 1550. MRD was successfully applied in 89% of the cases. The combined positive MRD values at day 33 and 78 of treatment allow the identification of high-risk patients in cases previously stratified by MRD using flow cytometry at day 15. The comparison between MRD determination by Ig/TCR rearrangements and FC showed excellent correlation. The present work constitutes a study of MRD by Ig/TCR carried out in a very significant number of patients consecutively diagnosed, treated within a homogeneous protocol and with excellent clinical follow-up.


Subject(s)
Humans , Child , Immunoglobulins , Gene Rearrangement, T-Lymphocyte , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Polymerase Chain Reaction , Neoplasm, Residual/genetics
2.
Article in Chinese | WPRIM | ID: wpr-880131

ABSTRACT

OBJECTIVE@#To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ.@*METHODS@#The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3@*RESULTS@#A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated.@*CONCLUSION@#The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.


Subject(s)
Humans , Leukocytes, Mononuclear , Lymphocyte Activation , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Up-Regulation
3.
Article in Chinese | WPRIM | ID: wpr-880128

ABSTRACT

B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar to those with childhood B-ALL, the rate of long-term disease-free survival (DFS) rate is significantly lower, once recurrence, the remission rate of routine chemotherapy is low and the prognosis is so poor. Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.


Subject(s)
Adult , Antigens, CD19 , Antigens, Surface , B-Lymphocytes , Burkitt Lymphoma , Child , Humans , Immunotherapy, Adoptive , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell
4.
Article in Chinese | WPRIM | ID: wpr-880069

ABSTRACT

T lymphoid malignancy is a group of highly heterogeneous hematological tumors. Disease recurrence and resistance to therapy are the common causes of failed treatment. Traditional therapy is radiotherapy and chemotherapy, although it has achieved great success. However, many patients still failed to survive following the treatment. With the introduction of monoclonal antibodies, immunotherapy and cellular therapy into clinical practice, the outcome of hematologic malignancies has been significantly improved. In particular, chimeric antigen receptor T cells (CAR-T) showed high efficacy in treating B-cell lymphoma and acute B lymphocytic leukemia and surpassed any previous therapeutic strategies. However, this treatment seldom succeeded in treating T cell malignancies. In this review, the history of CAR-T cells treating T cell malignancies, and the clinical trials, adverse events of previously reported were summarized briefly.


Subject(s)
Humans , Immunotherapy , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , T-Lymphocytes
5.
Frontiers of Medicine ; (4): 711-725, 2020.
Article in English | WPRIM | ID: wpr-880967

ABSTRACT

The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.


Subject(s)
Cell- and Tissue-Based Therapy , Humans , Immunotherapy, Adoptive , Lymphoma/therapy , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen
6.
Frontiers of Medicine ; (4): 786-791, 2020.
Article in English | WPRIM | ID: wpr-880947

ABSTRACT

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P < 0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.


Subject(s)
Cell- and Tissue-Based Therapy , Humans , Immunotherapy, Adoptive , Lymphoma, Non-Hodgkin/therapy , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen
8.
Blood Research ; : 274-281, 2019.
Article in English | WPRIM | ID: wpr-785538

ABSTRACT

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of diseases. Immune reconstitution is an important event that determines outcomes. The immune recovery of T cells relies on peripheral expansion of mature graft cells, followed by differentiation of donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. The aim of this study was to determine the role of TREC quantitation in predicting outcomes of human leucocyte antigen (HLA) identical allogenic HSCT.METHODS: The study was conducted on 100 patients receiving allogenic HSCT from an HLA identical sibling. TREC quantification was done by real time PCR using a standard curve.RESULTS: TREC levels were inversely related to age (P=0.005) and were significantly lower in patients with malignant diseases than in those with benign diseases (P=0.038). TREC levels could predict relapse as an outcome but not graft versus host disease (GvHD) and infections.CONCLUSION: Age and nature of disease determine the TREC levels, which are related to relapse.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Methods , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Receptors, Antigen, T-Cell , Recurrence , Siblings , T-Lymphocytes , Thymus Gland , Transplants
9.
Frontiers of Medicine ; (4): 69-82, 2019.
Article in English | WPRIM | ID: wpr-771259

ABSTRACT

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-γ and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.


Subject(s)
Cell Line, Tumor , Cytokines , Metabolism , Cytotoxicity, Immunologic , Genetic Engineering , HLA-A2 Antigen , Metabolism , Humans , Immunotherapy, Adoptive , Methods , Lymphocyte Activation , Receptors, Antigen, T-Cell , Genetics , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology
10.
Chinese Medical Journal ; (24): 1435-1440, 2019.
Article in English | WPRIM | ID: wpr-771214

ABSTRACT

BACKGROUND@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of high-grade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*METHODS@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*RESULTS@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*CONCLUSIONS@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.


Subject(s)
Adult , Aged , Female , Glioma , Genetics , Metabolism , Mortality , Therapeutics , Humans , Immunotherapy , Male , Middle Aged , Polymerase Chain Reaction , Receptors, Antigen, T-Cell , Chemistry , Genetics , Time Factors , Young Adult
11.
Article in Chinese | WPRIM | ID: wpr-773742

ABSTRACT

The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.


Subject(s)
Drugs, Chinese Herbal , HLA Antigens , Humans , Medicine, Chinese Traditional , Neoplasms , Allergy and Immunology , Receptors, Antigen, B-Cell , Receptors, Antigen, T-Cell
12.
Article in English | WPRIM | ID: wpr-772941

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.


Subject(s)
Adult , Antigens, CD19 , Metabolism , Bone Marrow , Metabolism , CD8-Positive T-Lymphocytes , Allergy and Immunology , Female , Gene Expression Regulation, Leukemic , Gene Regulatory Networks , Humans , Immunotherapy, Adoptive , Male , MicroRNAs , Genetics , Metabolism , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Allergy and Immunology , Therapeutics , RNA, Long Noncoding , Genetics , Metabolism , Receptors, Antigen, T-Cell , Transcription Factors , Metabolism , Transcriptome , Genetics
13.
Journal of Experimental Hematology ; (6): 1316-1320, 2019.
Article in Chinese | WPRIM | ID: wpr-775722

ABSTRACT

Abstract  Chimeric antigen receptor-T cell(CAR-T) is a kind of genetically engineered T cells that can express tumor antigen-specific receptors on its surface, and the modified T cells can be used for cancer therapy through targeting malignant tumor cells with its specific receptor and killing tumor cells with its cytotoxicity. CAR-T has been successfully applied to treat various hematological malignancies, such as ALL, CLL, NHL and MM. It is a feasible treatment for relapsed and refractory multiple myeloma (RRMM). The achievements of CAR-T in clinical trials have been widely reported, which is expected to be a therapy to prolong patients survival. In this review, the clinical application of CAR-T in the treatment of RRMM from the following aspects:different types of CAR-T and its curative efficacy, adverse effects, opportunities and challenges are summarized beriefly.


Subject(s)
Humans , Immunotherapy, Adoptive , Multiple Myeloma , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , T-Lymphocytes
14.
Journal of Experimental Hematology ; (6): 1353-1359, 2019.
Article in Chinese | WPRIM | ID: wpr-775714

ABSTRACT

OBJECTIVE@#To study the safety and effectiveness of humanized CD19-targeted CAR-T cells (hCART19s) for treatment of patients with refractory/relapsed (R/R) B-ALL.@*METHODS@#The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells. The patients received a single dose (1×10/kg) of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine.@*RESULTS@#Among the 15 patients, 13/14 (92.9%) evaluable patients achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) on day 30 after hCART19s infusion. At day 180 after the infusion, the overall survival rate was 73.3%, and the leukemia-free survival rate was 69.2%. The cumulative incidence of relapse was 24.5% and non-relapse mortality rate was 7.7%. During treatment,12/15 patients (80%) developed cytokine release syndrome (CRS) of grade 1-2, and 3 patients (20.0%) developed CRS of grade 3-5. Only one patient (6.7%) suffered from the reversible neurotoxicity.@*CONCLUSION@#hCART19s can effectively treat refractory/relapsed (R/R) adult and children with B-ALL, and the incidence of treatment-related CRS and neurotoxicity is low.


Subject(s)
Adult , Animals , Child , Humans , Leukemia, B-Cell , Therapeutics , Mice , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , T-Lymphocytes , Treatment Outcome
15.
Blood Research ; : 81-83, 2019.
Article in English | WPRIM | ID: wpr-763069

ABSTRACT

No abstract available.


Subject(s)
Hematologic Neoplasms , Receptors, Antigen, T-Cell
16.
Article in English | WPRIM | ID: wpr-761799

ABSTRACT

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.


Subject(s)
Animals , Biomarkers , Calcium , Calcium Signaling , Citric Acid , Citric Acid Cycle , Cytokines , Dermatitis, Atopic , Gene Ontology , Genome , Metabolism , Mice , Microarray Analysis , Mitochondria , Muscle Cells , Muscle Contraction , Muscle, Skeletal , Myoblasts , Myocardium , Oxidation-Reduction , Protein Interaction Maps , Pyroglyphidae , Receptors, Antigen, T-Cell , Skin
17.
Immune Network ; : e14-2019.
Article in English | WPRIM | ID: wpr-740214

ABSTRACT

Invariant NKT (iNKT) cells are a small subset of thymus-generated T cells that produce cytokines to control both innate and adaptive immunity. Because of their very low frequency in the thymus, in-depth characterization of iNKT cells can be facilitated by their enrichment from total thymocytes. Magnetic-activated cell sorting (MACS) of glycolipid antigen-loaded CD1d-tetramer-binding cells is a commonly used method to enrich iNKT cells. Surprisingly, we found that this procedure also dramatically altered the subset composition of enriched iNKT cells. As such, NKT2 lineage cells that express large amounts of the transcription factor promyelocytic leukemia zinc finger were markedly over-represented, while NKT1 lineage cells expressing the transcription factor T-bet were significantly reduced. To overcome this limitation, here, we tested magnetic-activated depletion of CD24⁺ immature thymocytes as an alternative method to enrich iNKT cells. We found that the overall recovery in iNKT cell numbers did not differ between these 2 methods. However, enrichment by CD24⁺ cell depletion preserved the subset composition of iNKT cells in the thymus, and thus permitted accurate and reproducible analysis of thymic iNKT cells in further detail.


Subject(s)
Adaptive Immunity , Cytokines , Leukemia , Methods , Natural Killer T-Cells , Receptors, Antigen, T-Cell , T-Lymphocytes , Thymocytes , Thymus Gland , Transcription Factors , Zinc Fingers
18.
Braz. j. med. biol. res ; 52(7): e8292, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011589

ABSTRACT

The thymus is a primary lymphoid organ responsible for the maturation of T cells as well as the immunological central tolerance. It is in the antenatal period and infancy that it plays its major role. In clinical practice, T cell receptor excision circles (TRECs) are considered a direct and reliable measure of the thymic function. TRECs are a by-product of DNA formation in gene rearrangement of T cell receptors. They are stable and they do not duplicate during mitosis, representing the recent emigrant T cells from the thymus. Despite their importance, TRECs have been neglected by physicians and there is a lack of data regarding thymic function during infancy of healthy children. In order to evaluate thymic function in the first years of life, we propose measuring TRECs as a valuable tool. One hundred and three blood samples from children and adolescents between 3 months and 20 years of age were analyzed. The mean TRECs count was 136.77±96.7 copies of TRECs/μL of DNA. The individuals between 0 and 5 years of age had significantly higher TRECs values than those between 10 and 20 years of age. No significant difference was observed in TRECs values among age groups below 5 years of age. An inverse correlation between TRECs and age was found (r=0.3 P=0.003). These data highlight and validate the evidence of decreased thymus function with age, even during infancy. Awareness should be raised with this important albeit ignored organ.


Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Young Adult , Thymus Gland/physiology , Receptors, Antigen, T-Cell/physiology , Reference Values , Thymus Gland/cytology , Biomarkers/blood , Gene Rearrangement, T-Lymphocyte , Reproducibility of Results
19.
Chinese Journal of Biotechnology ; (12): 2339-2349, 2019.
Article in Chinese | WPRIM | ID: wpr-781634

ABSTRACT

Chimeric antigen receptor T (CAR-T) cell therapy, which adoptively transfers engineered T cells expressing synthetic receptors to target specific antigens, has achieved great clinical success in treating hematological malignancies. Though FDA has approved two CAR-T products, CAR-T therapy can cause some side effects, such as cytokine release syndrome (CRS), neurotoxicity and B cell aplasia. Meanwhile, lacking tumor specific antigen and the suppressive tumor environment limit the efficacy of CAR-T therapy in solid tumor. This review focuses on the structural components, clinical applications and synthetic biology approaches on CAR-T cell design, and summarizes the challenges and perspectives of CAR-T therapy as a revolutionary cancer immunotherapy.


Subject(s)
Cell- and Tissue-Based Therapy , Child , Humans , Immunotherapy , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , T-Lymphocytes
20.
Journal of Experimental Hematology ; (6): 1604-1609, 2018.
Article in Chinese | WPRIM | ID: wpr-773049

ABSTRACT

OBJECTIVE@#To investigate the efficacy of CD19-targeted chimeric antigen receptor T-cell (CD19-CAR T) in the treatment of patients with refractory relapsed B cell acute lymphocyte leukemia(B-ALL).@*METHODS@#The efficacy and safety of CD19-CAR T cells in treatment of patients with refractory relapsed B-ALL from January 2015 to July 2017 in the Department of Hematology of Peking University Third Hospital were analyzed retrospectively.@*RESULTS@#A total of 10 patients were included in this analysis, all of which were consistent with the diagnosis of refractory relapsed B-ALL, and the immunophenotype of leukemia cells was CD19 positive. After treatment with CD19-CAR T cells, the overall response rate(ORR) on day 28 was 70%. Among them, 6 cases reached complete remission(CR), 1 case reached partial remission(PR). The rate of CR on day 90 was 30%.@*CONCLUSION@#CD19-CAR T cells are effective in the treatment of refractory relapsed B-ALL, and the adverse reactions are controllable.


Subject(s)
Acute Disease , Antigens, CD19 , B-Lymphocytes , Humans , Immunotherapy, Adoptive , Leukemia, B-Cell , Receptors, Antigen, T-Cell , Recurrence , Retrospective Studies , T-Lymphocytes
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