A5046633288- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Nanowire Synthesis and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Advancements in Semiconductor Devices and Circuit Design
- Biosimilars and Bioanalytical Methods
- RNA regulation and disease
- Virus-based gene therapy research
- Cancer Research and Treatments
- Nanofabrication and Lithography Techniques
- Toxin Mechanisms and Immunotoxins
- Endoplasmic Reticulum Stress and Disease
Gadeta (Netherlands)
2021-2023
The Netherlands Cancer Institute
2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2014-2021
Cancer Center Amsterdam
2021
Amsterdam University Medical Centers
2019-2021
Vrije Universiteit Amsterdam
2021
Utrecht University
2016
University Medical Center
2015
University Medical Center Utrecht
2012-2014
Targeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells tumor expressing high TAA levels while sparing low normal tissues. However, decreasing the of CAR-target binding compromise overall antitumor Here, we demonstrate prime importance type intracellular signaling on function low-affinity CAR-T cells.We...
Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears suitable target antibody therapy. Prompted by this, we used three different sequences to generate second-generation retroviral CD38-chimeric receptor constructs which transduced from healthy donors and patients. We then evaluated the preclinical efficacy safety cells. Irrespective donor sequence,...
Due to the CD1d restricted recognition of altered glycolipids, Vα24-invariant natural killer T (iNKT) cells are excellent tools for cancer immunotherapy with a significantly reduced risk graft-versus-host disease when applied as off-the shelf-therapeutics across Human Leukocyte Antigen (HLA) barriers. To maximally harness their therapeutic potential multiple myeloma (MM) treatment, we here armed iNKT chimeric antigen receptors (CAR) directed against MM-associated CD38 and plasma cell...
Recent clinical advances with chimeric antigen receptor (CAR) T cells have led to the accelerated approval of CD19-CARs treat acute lymphoblastic leukemia. The CAR cell therapy is nevertheless associated toxicities, especially if CARs are not entirely tumor-specific. Therefore, strategies for controlling activity required improve their safety profile. Here, by using multiple myeloma (MM)-associated CD38 molecule as target molecule, we tested feasibility and utility a doxycycline (DOX)...
Abstract Purpose: The microenvironment of multiple myeloma (MM) can critically impair therapy outcome, including immunotherapies. In this context, we have earlier demonstrated that bone marrow mesenchymal stromal cells (BMMSC) protect MM against the lytic machinery MM-reactive cytotoxic T (CTL) and daratumumab-redirected natural killer (NK) through upregulation antiapoptotic proteins Survivin Mcl-1 in cells. Here, investigated significance mode immune escape on engineered to express chimeric...
Currently ~50% of patients with a diagnosis high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression represents major challenge T cell-mediated immunotherapy. Here, we propose novel cell-based approach neuroblastoma, based on use TEG002, αβ-T cells engineered express defined γδ-T cell receptor, which can recognize and kill target independent MHC-I. In co-culture...
Meeting abstracts Adoptive transfer of T cells transduced with tumor-reactive Chimeric Antigen Receptors (CARs) is a promising strategy for cancer immunotherapy. The CD38 molecule, its high and homogenous expression on Multiple Myeloma (MM) cells, appears suitable target antibody therapy
Abstract Immunotherapy development for solid tumors remains challenging, partially due to a lack of reproducible, cost-effective in vitro three-dimensional (3D) models mimic the heterogeneous and complex tumor microenvironment. Here, we investigate cellular anti-tumor reactivity αβ T cells engineered express defined γδ TCR (TEG A3). For that purpose, developed 3D cytotoxicity assay targeting cell line–derived spheroids or patient-derived organoids formed serum-free media. Tumor lysis by TEG...
<h3>Background</h3> Currently ~50% of patients with the diagnosis high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but low MHC-I expression represents a major challenge T cell-mediated immunotherapy. Here, we propose novel cell-based approach neuroblastoma, based on use TEG002, αβ-T cells engineered express defined γδ-T cell receptor, which thought recognize and kill target independent...
Abstract Broad application of cell therapies like CAR-T have been hampered by a lack tumor-specific targets. Gadeta leverages the natural HLA-independent tumor recognition capabilities γδTCRs combined with proliferative capacity and robust killing αβT cells to develop therapies. γδT expressing Vγ9Vδ2 TCRs are most common subtype found in peripheral blood. They sense presence phosphoantigens (pAgs) upregulated malignant due dysregulated mevalonate pathway. The TCR expressed GDT002 was...
<p>Table providing information on scFv sequences CARs. Figures data CAR T cell phenotype, BMMSC survival, target antigen expression, cytotoxic mediator measurements, Survivin and Mcl-1 expression in MM cells, effector vivo efficacy of BCMA-CAR cells.</p>
<p>Supplementary methods and data</p>
<p>Table providing information on scFv sequences CARs. Figures data CAR T cell phenotype, BMMSC survival, target antigen expression, cytotoxic mediator measurements, Survivin and Mcl-1 expression in MM cells, effector vivo efficacy of BCMA-CAR cells.</p>
<div>AbstractPurpose:<p>The microenvironment of multiple myeloma (MM) can critically impair therapy outcome, including immunotherapies. In this context, we have earlier demonstrated that bone marrow mesenchymal stromal cells (BMMSC) protect MM against the lytic machinery MM-reactive cytotoxic T (CTL) and daratumumab-redirected natural killer (NK) through upregulation antiapoptotic proteins Survivin Mcl-1 in cells. Here, investigated significance mode immune escape on engineered...
<div>AbstractPurpose:<p>Targeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells tumor expressing high TAA levels while sparing low normal tissues. However, decreasing the of CAR-target binding compromise overall antitumor Here, we demonstrate prime importance type intracellular signaling on...
<div>AbstractPurpose:<p>The microenvironment of multiple myeloma (MM) can critically impair therapy outcome, including immunotherapies. In this context, we have earlier demonstrated that bone marrow mesenchymal stromal cells (BMMSC) protect MM against the lytic machinery MM-reactive cytotoxic T (CTL) and daratumumab-redirected natural killer (NK) through upregulation antiapoptotic proteins Survivin Mcl-1 in cells. Here, investigated significance mode immune escape on engineered...
<div>AbstractPurpose:<p>Targeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells tumor expressing high TAA levels while sparing low normal tissues. However, decreasing the of CAR-target binding compromise overall antitumor Here, we demonstrate prime importance type intracellular signaling on...
<p>Supplementary methods and data</p>
Abstract Immunotherapy with innate immune cells has recently evoked a broad interest as novel treatment option for cancer patients. γ9δ2T-cells are an emerging cell population strong anti-tumor-reactivity and promising candidate interventions. Especially γ9δ2T-cell receptors (TCR) which recognize panel of tumor high avidity clinically attractive since αβT-cells can be efficiently redirected against variety by introducing γ9δ2TCR. Here we demonstrate that distinct γ9δ2TCRs mediate different...