Search results for: Recombinant Human TNFRSF9 Proteins
#28246194 2017/03/01 Save this To Up
Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia.We and others previously reported potent antileukemia efficacy of CD123-redirected chimeric antigen receptor (CAR) T cells in preclinical human acute myeloid leukemia (AML) models at the cost of severe hematologic toxicity. This observation raises concern for potential myeloablation in patients with AML treated with CD123-redirected CAR T cells and mandates novel approaches for toxicity mitigation. We hypothesized that CAR T-cell depletion with optimal timing after AML eradication would preserve leukemia remission and allow subsequent hematopoietic stem cell transplantation. To test this hypothesis, we compared 3 CAR T-cell termination strategies: (1) transiently active anti-CD123 messenger RNA-electroporated CART (RNA-CART123); (2) T-cell ablation with alemtuzumab after treatment with lentivirally transduced anti-CD123-4-1BB-CD3ζ T cells (CART123); and (3) T-cell ablation with rituximab after treatment with CD20-coexpressing CART123 (CART123-CD20). All approaches led to rapid leukemia elimination in murine xenograft models of human AML. Subsequent antibody-mediated depletion of CART123 or CART123-CD20 did not impair leukemia remission. Time-course studies demonstrated that durable leukemia remission required CAR T-cell persistence for 4 weeks prior to ablation. Upon CAR T-cell termination, we further demonstrated successful hematopoietic engraftment with a normal human donor to model allogeneic stem cell rescue. Results from these studies will facilitate development of T-cell depletion strategies to augment the feasibility of CAR T-cell therapy for patients with AML.
1238 related Products with: Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia.anti Transferrin receptor Interferon-a Receptor Typ anti CD38 Hematopoietic p Mouse Anti-Human CD34 Tar Rat monoclonal anti mouse Rat monoclonal anti mouse CELLKINES Natural Human I Human Tumor Necrosis Fact Goat Anti-Human HMGB3 HMG Goat Anti-Human F2R PAR1, Mouse Anti-Human Interleu Mouse Anti-Human Thyroid
#27887866 2016/11/26 Save this To Up
Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications.
2665 related Products with: Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.anti CD16 NK cells, monoc anti CD45 RA B cells, T c anti Transferrin receptor Human Cardiac Microvascul Rabbit B cell leukemia ly Hairy Cell Leukemia; Clo Hairy Cell Leukemia; Clo CD5 (Mantel Cell Lymphom CD5 (Mantel Cell Lymphom CD5 (Mantel Cell Lymphom Hairy Cell Leukemia; Clo CD5 (Mantel Cell Lymphom
#27760761 2016/10/20 Save this To Up
MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults.Attenuated poxvirus modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding 3 immunodominant cytomegalovirus (CMV) antigens, which stimulates a host antiviral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination). Three escalating dose levels (DL) were administered IM in 8 subjects/DL, with an identical booster injection 28 days later and 1-year follow-up. Vaccinations at all DL were safe with no dose-limiting toxicities. No vaccine-related serious adverse events were documented. Local and systemic reactogenicity was transient and self-limiting. Robust, functional, and durable Triplex-driven expansions of CMV-specific T cells were detected by measuring T-cell surface levels of 4-1BB (CD137), binding to CMV-specific HLA multimers, and interferon-γ production. Marked and durable CMV-specific T-cell responses were also detected in Triplex-vaccinated CMV-seronegatives, and in DryVax-vaccinated subjects. Long-lived memory effector phenotype, associated with viral control during CMV primary infection, was predominantly found on the membrane of CMV-specific and functional T cells, whereas off-target vaccine responses activating memory T cells from the related herpesvirus Epstein-Barr virus remained undetectable. Combined safety and immunogenicity results of MVA in allogeneic hematopoietic stem cell transplant (HCT) recipients and Triplex in healthy adults motivated the initiation of a placebo-controlled multicenter trial of Triplex in HCT patients. This trial was registered at www.clinicaltrials.gov as #NCT02506933.
1075 related Products with: MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults.Recombinant Viral antige Glucagon ELISA KIT, Rat G Leptin ELISA Kit, Rat Lep Signal transduction antib Chromatin Transcription P TGF-Beta Signaling Phosph Tyrosine Kinase Adaptors Th1 Th2 Th17 (Human) Anti Th1 Th2 Th17 (Human) Anti CMV IgG (quantitative) CMV IgM (capture) Octyl â D 1 thioglucopyr
#27745631 2016/10/17 Save this To Up
Evaluating the skin in patients undergoing chimeric antigen receptor modified T-cell therapy.
1704 related Products with: Evaluating the skin in patients undergoing chimeric antigen receptor modified T-cell therapy.anti Transferrin receptor T-Cell Receptor Signaling Dog Receptor-binding canc Mouse AntiT cell receptor Mouse Anti DO11.10 T cell Skin squamous cell carcin HIV 1 intergase antigen. anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl CELLKINES Natural Human I CELLKINES INTERLEUKIN 2 (
#27598655 2016/09/07 Save this To Up
Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86. A 21-day culture of PBMCs with this method yielded nearly 20,000-fold expansion of CIKZ cells with γδ T cells making up over 20% of the expanded population. The expanded CIKZ cells exhibited antitumor cytotoxicity and could be modified to express anti-CD19 chimeric antigen receptor (CAR), anti-CEA CAR, and anti-HER2 CAR to enhance their specificity and cytotoxicity against CD19-, CEA-, or HER2-positive tumor cells. The tumor inhibitory activity of anti-CD19 CAR-modified CIKZ cells was further demonstrated in vivo in a Raji tumor mouse model. The findings herein substantiate the feasibility of co-expanding CIK and γδ cells for adoptive cellular immunotherapy applications such as CAR T-cell therapy against cancer.
1390 related Products with: Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.Macrophage Colony Stimula Macrophage Colony Stimula Recombinant Human OPG TNF Recombinant Human OPG TNF Recombinant Human THPO [f Glucagon ELISA KIT, Rat G Leptin ELISA Kit, Rat Lep anti CD38 Hematopoietic p anti Transferrin receptor Wnt Signaling Pathway TCF Mitochondria GFP Tag Huma Plasma Membrane GFP Tag H
#27548616 2016/08/23 Save this To Up
Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.
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#27365313 2016/07/08 Save this To Up
Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease.Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.
2473 related Products with: Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease.anti Transferrin receptor MOUSE ANTI BORRELIA BURGD TNFRSF1B - Goat polyclona anti CD38 Hematopoietic p Dog Receptor-binding canc Mouse AntiReceptor Tyrosi Mouse AntiReceptor Tyrosi Mouse AntiMer Receptor Ty Mouse Anti Progesterone R Mouse AntiProgesterone Re Mouse Anti Progesterone R Mouse Anti Progesterone R
#27049955 2016/04/07 Save this To Up
4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on conventional CD4+ T cells (Tconvs) overcomes the suppression mediated by naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs). The mechanistic basis of this observation has remained largely unknown. Herein we show that Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB signaling as a key circuit that regulates physical and functional equilibrium between Tregs and Tconvs with important implications for immunotherapy for indications where a fine balance between Tregs and Teffs plays a decisive role.
1420 related Products with: 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.CELLKINES Natural Human I Glucagon ELISA KIT, Rat G Leptin ELISA Kit, Rat Lep Cultrex 24 Well BME Cell Cultrex 24 Well Laminin I Cultrex 24 Well Collagen Cultrex 24 Well Collagen anti CD38 Hematopoietic p Wnt Signaling Pathway TCF Kidney clear cell carcino Mouse Anti-Human Fibrobla Esophagus squamous cell c
#27004934 2016/03/29 Save this To Up
An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression.Previous studies have shown promising results when using an agonistic anti-4-1BB antibody treatment against established tumors. While this is promising, this type of treatment can induce severe side effects. Therefore, we decided to incorporate the membrane form of 4-1BB ligand (4-1BBL) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA). The Ii adjuvant increases and prolongs TAA specific CD8+ T cells as previously shown and local expression of 4-1BBL was chosen to avoid the toxicity associated with systemic antibody administration. Furthermore, adenovirus encoded 4-1BBL expression has previously been successfully used to enhance responses toward Plasmodium falciparum and Influenza A antigens. We showed that the incorporation of 4-1BBL in the adenovirus vector led to surface expression of 4-1BBL on antigen presenting cells, but it did not enhance T cell responses in mice towards the Ii linked antigen. In tumor-bearing mice, our vaccine was found to decrease the frequency of TAA specific CD8+ T cells, but this difference did not alter the therapeutic efficacy. In order to reconcile our findings with the previous reports of increased anti-cancer efficacy using systemically delivered 4-1BB agonists, we incorporated a secreted version of 4-1BBL (Fc-4-1BBL) in our vaccine and co-expressed it with the Ii linked to TAA. In tumor bearing mice, this vaccine initially delayed tumor growth and slightly increased survival compared to the vaccine expressing the membrane form of 4-1BBL. Accordingly, secreted 4-1BBL co-encoded with the Ii linked antigen may offer a simplification compared to administration of drug and vaccine separately.
1287 related Products with: An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression.TNFRSF1B - Goat polyclona Tumor necrosis factor (TN Multiple organ cancer tis Tonsil disease spectrum ( CA125, Ovarian Cancer An CA125, Ovarian Cancer An CA125, Ovarian Cancer An Toxoplasma gondii MIC 3 r Toxoplasma gondii P24 (GR Toxoplasma gondii P29 (GR Toxoplasma gondii P30 (SA serologically defined col
#26885860 2016/02/18 Save this To Up
Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, we report the influence of signaling domains of coreceptors CD28 and 4-1BB on the metabolic characteristics of human CAR T cells. Inclusion of 4-1BB in the CAR architecture promoted the outgrowth of CD8(+) central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies.
2946 related Products with: Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.Leptin ELISA Kit, Rat Lep TGF-Beta Signaling Phosph H. Pylori antigen test ca Glucagon ELISA KIT, Rat G Wnt Signaling Pathway TCF Signal transduction antib AKT PKB Signaling Phospho AMPK Signaling Phospho-Sp Chromatin Transcription P ErbB Her Signaling Phosph ERK Signaling Phospho-Spe GPCR Signaling to MAPK ER
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