• Janssen represents the ideal partner for this product candidate, given their track record of successfully developing and commercializing transformative oncology therapies and their experience in the B-cell malignancy area. (cnbc.com)
  • Upfront use of nelarabine plus standard Children's Oncology Group-augmented Berlin-Frankfurt-Münster (aBFM) chemotherapy boosted survival rates in children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic leukemia (T-LL), according to the results of a large phase III federally funded trial to be presented at the 2018 ASCO Annual Meeting. (ascopost.com)
  • The success of bortezomib (VELCADE) for the treatment of multiple myeloma and relapsed mantle cell lymphoma validated the proteasome as an oncology target. (aacrjournals.org)
  • Different B-cell malignancies share common molecular pathways, which is why they may benefit from the same pathway-specific targeted treatment. (hindawi.com)
  • Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia," Cancer Cell , vol. 1, no. 1, pp. 75-87, 2002. (hindawi.com)
  • Recent reports have shown that the disturbed redox homeostasis in B-cell malignancies is regulated by cancer-specific signaling pathways and therefore varies between the individual subtypes. (ovid.com)
  • Inhibition of the proteasome leads to stabilization and accumulation of these proteasome substrates, resulting in concomitant activation of pro- and antiproliferative signals, disruption of cell-cycle regulation, and, ultimately, activation of apoptotic pathways and cell death ( 3, 4 ). (aacrjournals.org)
  • 1. Patients with histologic proof of incurable T-cell malignancy or Hodgkin's disease, and not eligible for existing/higher priority protocols. (knowcancer.com)
  • In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish," Proceedings of the National Academy of Sciences of the United States of America , vol. 101, no. 19, pp. 7369-7374, 2004. (hindawi.com)
  • Therefore, most clinical applications have resulted in limited in vivo expansion and persistence of CAR-modified T cells resulting in disappointing clinical activity 3 , 4 . (jcancer.org)
  • By inclusion of the 4-1BB signaling domain, in vitro tumor cell killing, and in-vivo anti-tumor activity and persistence of CART-19 cells in a murine xenograft model of human ALL is greatly enhanced 7 . (jcancer.org)
  • Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third generation CARs, including various costimulatory molecules, resulted in enhanced T-cell persistence and sustained antitumor activity in both in vitro and in vivo mouse models as well as clinical trials. (nih.gov)
  • Determine duration of in vivo survival of tanCART-19/20 cells. (clinicaltrials.gov)
  • Finally, by integrating recent data on venetoclax-monotherapy clinical activity with the expression of BCL2-family members involved in the venetoclax response, we determined that the ratio (BCL2 + BCL2L11 + BAX)/BCL2L1 was the strongest predictor of venetoclax response for mature B cell malignancies in vivo . (frontiersin.org)
  • Knocking out CD7 doesn't seem to have any impact on the expansion or trafficking of these T cells in vivo," Dr. DiPersio said. (mdedge.com)
  • Preclinical studies showed that inclusion of potent signaling molecules improves the antitumor activity of genetically modified T cells. (jcancer.org)
  • We sequenced the tumor-specific immunoglobulin heavy chain variable region fragment, including complementarity-determining regions 2 and 3, of forty-seven consecutive patients with a B-cell malignancy enrolled in idiotype vaccine clinical trials. (cun.es)
  • However, CCR5 staining was seen in three of five cases of HCL, representing the first example of cross-lineage aberrant chemokine receptor expression in malignant haemopoietic cells. (nih.gov)
  • In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases spleen tyrosine kinase and phosphatidylinositol 3-kinase and inhibits vascular endothelial growth factor A secretion by tumor cells, inducing cancer cell apoptosis and blocking angiogenesis in the microenvironment. (bloodjournal.org)
  • RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/20 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time. (clinicaltrials.gov)
  • Recent findings reveal important differences in redox homeostasis within the distinct subsets of B-cell-derived malignancies that can be therapeutically exploited to improve existing treatment and to overcome drug resistance. (ovid.com)
  • Determine the relative subsets of tanCART-19/20 T cells (Tcm, Tem, and Treg). (clinicaltrials.gov)
  • Conclusion: Selective PI3K pathway inhibition, particularly at the level of mTOR, results in cytostatic, and at higher concentrations cytotoxic, responses in haematological malignancies. (aacrjournals.org)
  • Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. (aacrjournals.org)
  • We showed that its biologically active form MLN2238 has improved pharmacodynamics and antitumor activity compared with bortezomib in various B-cell lymphoma models and showed that only MLN2238 alleviated osteolytic bone disease in our PCM model. (aacrjournals.org)
  • Translocations involving an immunoglobulin (IG) locus are a recurring theme in B cell neoplasia. (lu.se)
  • article{397dcdda-a631-4af5-9423-af25bb8cac42, abstract = {Translocations involving an immunoglobulin (IG) locus are a recurring theme in B cell neoplasia. (lu.se)
  • The majority of B cell malignancies arise within the germinal centre, a stage of B cell differentiation associated with significant genetic instability. (ul.ie)
  • B cell differentiation is a tightly controlled process that leads to the generation and selection of memory B cells and antibody-secreting plasma cells ( 1 , 2 ). (frontiersin.org)
  • Additionally, an interleukin-7 molecule called NT-I7 has been shown to enhance CAR T-cell proliferation, differentiation, and tumor killing in a mouse model of a T-cell malignancy. (mdedge.com)
  • Combination of Blinatumomab and Vincristine Sulfate Liposome Injection for Treatment of Relapsed Philadelphia Chromosome Positive B-cell Acute Lymphoblastic Leukemia. (bioportfolio.com)
  • Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia," Journal of Experimental Medicine , vol. 208, no. 18, pp. 1595-1603, 2011. (hindawi.com)
  • Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse," Journal of Experimental Medicine , vol. 208, no. 4, pp. 653-661, 2011. (hindawi.com)
  • Dr. DiPersio noted that CD7 is expressed on 98% of T-cell acute lymphoblastic leukemias (T-ALLs), 24% of acute myeloid leukemias, natural killer (NK) cells, and T cells. (mdedge.com)
  • MicroRNAs have the potential to be useful biomarkers in the development of individualized treatment since they are easy to detect, are relatively stable during sample handling, and are important determinants of cellular processes controlling pathogenesis, progression, and response to treatment of several types of cancers including B-cell malignancies. (hindawi.com)
  • The contribution of the oncogenic Epstein-Barr virus to the pathogenesis of B cell malignancies. (ul.ie)
  • Here, we review a decade-long exploration of the contribution of cyclic-AMP and PDE4 to the pathogenesis of B-cell lymphoma, 5 ⇓ ⇓ ⇓ - 9 culminating with the first-in-cancer clinical trial of a PDE4 inhibitor in advanced B-cell malignancies. (bloodjournal.org)
  • The Epstein-Barr virus (EBV) is a human herpesvirus that can colonise germinal centre B cells as part of its natural life cycle in the asymptomatic host. (ul.ie)
  • However, EBV is associated with the development of germinal centre derived B cell malignancies. (ul.ie)
  • Expansion groups of up to 12 subjects for Germinal center B-cell (GCB) DLBCL and Non-GCB DLBCL to take a fixed dose of acalabrutinib and ACP-319. (clinicaltrials.gov)
  • Until recently, development of this technology has been limited by lack of efficient T cell culture systems and gene transfer techniques. (jcancer.org)
  • Against the background of what one knows about [email protected] involvement in lymphatic malignancies, it is difficult to envisage a fusion gene with qualitatively altered protein product as the crucial pathogenetic outcome of the translocation. (lu.se)
  • Lastly, attention is drawn to recent reports of effective treatment modalities involving prooxidative agents and interfering with redox homeostasis provided by stromal cells. (ovid.com)
  • Agents were studied in a panel of lymphoma and myeloma cell lines, in normal PBMCs and in primary tumours cultured with stromal cells. (aacrjournals.org)
  • High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion," PLoS One , vol. 5, no. 12, Article ID e15688, 2010. (hindawi.com)
  • The researchers created UCART7 by using CRISPR/Cas9 to delete CD7 and TRAC from allogeneic T cells and following this with lentiviral transduction with a third-generation CD7-CAR. (mdedge.com)
  • The effect of these compounds in primary mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia and myeloma samples was variable, both between and within tumour types, possibly due to differences in basal PI3K pathway activity. (aacrjournals.org)
  • Antibody-drug conjugates (ADCs) consisting of mcMMAF or vcMMAE displayed typical PK characteristics when tested in rodents and both compounds were equally effective when administered to mice xenografted with various NHL tumor types, including Ramos (Burkitt), DoHH2 (Mantle Cell) and a model of ALL (Nalm-6). (aacrjournals.org)
  • Here, we evaluated the investigational proteasome inhibitor MLN9708 in a variety of mouse models of B-cell and plasma cell malignancies (PCM), including traditional tumor xenograft models and genetically engineered mouse models. (aacrjournals.org)
  • We highlight advances in the use of CARs in the treatment of B-cell malignancies and future challenges in the use of adoptive therapy with CAR-engineered T cells. (nih.gov)
  • Information provided about the pediatric program includes the stem cell collection, conditions treated, and treatment areas. (dmoztools.net)
  • Histologically documented with histopathological diagnosis from biopsy, T/NK-cell malignancies (WHO classification). (knowcancer.com)
  • Diagnosis of a b-cell malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO). (clinicaltrials.gov)
  • Importantly, it is not expressed on pluripotent marrow stem cells 5 . (jcancer.org)
  • An organisation for those with a professional interest in stem cell transplantation, in clinical collaboration and the development of clinical trials in this field. (dmoztools.net)
  • NMDP research program focuses on improving clinical outcomes of blood stem cell transplantation. (dmoztools.net)
  • Promotes the exchange of information and development of standards to facilitate the exchange of hematopoietic stem cells (HSC) across international borders. (dmoztools.net)
  • RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. (bioportfolio.com)
  • MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. (bioportfolio.com)
  • MLN9708 (Millennium Pharmaceuticals, Inc.) is an investigational small-molecule proteasome inhibitor currently being developed for a broad range of human malignancies ( 8, 9 ). (aacrjournals.org)
  • Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus type 1 (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseases including very aggressive adult T-cell lymphoma (ATL), HTLV-I-associated myelopathy, uveitis, Strongyloides stercoralis hyper-infection and some other diseases. (wikipedia.org)
  • The human genome may encode over 1000 miRNAs, which are abundant in many mammalian cell types and appear to target about 60% of the genes of humans and other mammals. (wikipedia.org)
  • A year later, the lin-4 and let-7 RNAs were found to be part of a large class of small RNAs present in C. elegans, Drosophila and human cells. (wikipedia.org)
  • The present review elucidates the potential of miR-155 as a diagnostic, prognostic, or predictive biomarker in B-cell malignancies using a systematic search strategy to identify relevant literature. (hindawi.com)