A5005504613- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Nanowire Synthesis and Applications
- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Biosimilars and Bioanalytical Methods
- Reproductive System and Pregnancy
- Chronic Lymphocytic Leukemia Research
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Retinoids in leukemia and cellular processes
National Institutes of Health
2016-2025
National Institutes of Health Clinical Center
2017-2025
National Cancer Institute
2013-2025
Cellular Research (United States)
2022
Novartis (United States)
2021
Center for Cancer Research
2013-2016
University of Minnesota
2008-2014
University of Minnesota Medical Center
2010
Masonic Cancer Center
2010
Cancer Research Center
2010
Preventing trafficking of myeloid-derived suppressor cells to the tumor site enhances efficiency checkpoint blockade.
PURPOSE Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative antigen, represents alternate strategy. We report outcomes on the largest patient cohort treated CD22 chimeric antigen receptor (CAR) T cells. PATIENTS AND METHODS conducted a single-center, phase I, 3 + dose-escalation trial large expansion that tested CD22-targeted CAR cells for children and...
Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies treat pediatric sarcomas. observed 18 (100%) osteosarcomas, 2 15 (13%) rhabdomyosarcomas, 7 35 (20%) Ewing sarcomas expressed GD2....
Abstract Purpose: Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority post-CD22 CART remissions are short and associated reduction expression. We evaluate implications low density on activity propose mechanisms to overcome escape. Experimental Design: Using ALL cell lines variable expression, we cytokine profile, cytotoxicity, vivo functionality setting develop a...
Significance Many genes have been shown to influence the risk of developing multiple sclerosis (MS); however, biological processes responsible are not clear. We found that a genetic polymorphism associated with increased MS is for potentiating effects cytokine named interleukin (IL)-7 by securing its availability and bioactivity over time. This effect was mediated an isoform IL-7 receptor circulates at high levels in blood. important factor T-cell maturation proliferation, and, hence,...
Abstract Metastatic tumors have been shown to establish microenvironments in distant tissues that are permissive disseminated tumor cells. Hematopoietic cells contribute this microenvironment, yet the precise initiating events responsible for establishing pre-metastatic niche remain unclear. Here, we tracked developmental fate of hematopoietic stem and progenitor (HSPC) tumor-bearing mice. We show a primary drives expansion HSPCs within bone marrow their mobilization bloodstream. Treatment...
As clinical applications for chimeric antigen receptor T cell (CART) therapy extend beyond early phase trials, commercial manufacture incorporating cryopreservation steps becomes a logistical necessity. The effect of on CART characteristics is unclear. We retrospectively evaluated the product release criteria and in vivo 158 autologous products from 6 single-center trials. Further, 3 healthy donor manufacturing runs, we prospectively identified differentially expressed surface markers gene...
With investigators looking to expand engineered T cell therapies such as CAR-T new tumor targets and patient populations, a variety of manufacturing platforms have been developed scale capacity using closed and/or automated systems. Such are particularly useful for solid targets, which typically require higher doses. Although phenotype function key attributes that often correlate with therapeutic efficacy, how influence the final product is currently unknown. We compared 4 commonly used...
Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment hematologic malignancies have been promising, but CAR yields variable. This variability is due in part to contamination PBMC with monocytes and granulocytes. Counter-flow elutriation allows closed system separation lymphocytes We investigated use enriched using manufacturing 8 CD19- 5 GD2-CAR products. When compared concentrates,...
Chimeric antigen receptor T-cells (CART) are active in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), but relapse remains a substantial challenge. Reinfusion with the same CART product (CART2) patients suboptimal response or positive following first infusion (CART1) represents potential treatment strategy, though early experiences suggest limited efficacy of CART2 CD19 targeting. We report on our experience across host novel CAR T-cell trials. This was retrospective...
Abstract Previously we demonstrated that SHIP−/− mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study show splenocytes and lymph node cells are poor stimulators of T cell responses cause GvHD. Intriguingly, prime naive to peptide epitopes, but, conversely, partially impaired for priming whole Ag. However, dendritic (DC) purified from targets, Ag as effectively SHIP+/+ DC. These findings point an extrinsic effect on DC...
Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are most commonly used in manufacturing process. However, integration pattern these viral subsequent effect on products is still unclear.We modified sites analysis (VISA) pipeline to evaluate events around whole genome pre-infusion products. We compared differences between lentiviral also explored whether correlated...