A5075718499- CAR-T cell therapy research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Nanowire Synthesis and Applications
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Advancements in Semiconductor Devices and Circuit Design
- HER2/EGFR in Cancer Research
- Graphene and Nanomaterials Applications
- Glycosylation and Glycoproteins Research
Miltenyi Biotec (Germany)
2016-2024
Abstract Acute myeloid leukemia (AML) is a malignant disorder derived from neoplastic progenitor cells characterized by abnormal proliferation and differentiation. Although novel therapeutics have recently been introduced, AML remains therapeutic challenge with insufficient cure rates. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T were which showed outstanding clinical activity against B-cell malignancies including acute lymphoblastic (ALL). However,...
Abstract Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR cells) is a promising principle to overcome the limited activity canonical CAR against solid cancers. Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting directed ganglioside GD2 with CAR-inducible IL18 enhance their activation response and cytolytic effector functions in tumor microenvironment. To allow stratification patients according expression, we...
Genetic engineering is an important tool for redirecting the function of various types immune cells and their use therapeutic purpose. Although NK have many beneficial features, genetic targeted therapy focuses mostly on T cells. One major obstacles cell immunotherapy lack efficient method gene transfer. Lentiviral vectors been proven to be a safe engineering, however lentiviral transduction inefficient We show in this study that pseudotyped with modified baboon envelope glycoprotein can...
Cell and gene therapies are finally becoming viable patient treatment options, with both T cell- hematopoietic stem cell (HSC)-based being approved to market in Europe. However, these therapies, which involve the use of viral vector modify target cells, expensive there is an urgent need reduce manufacturing costs. One major cost factor production itself, therefore improving modification efficiency could significantly amount required per patient. This study describes a transduction enhancing...
A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality extracellular spacer module. However, several studies have elucidated membrane proximal epitopes are best targeted through CARs comprising long spacers, while short exhibit highest activity on distal epitopes. This finding can be explained by requirement to an optimal distance between effector T cell and target cell. Commonly used domains CH2-CH3 IgG molecules. containing these spacers...
As chimeric antigen receptor (CAR) T cell therapy continues to gain attention as a valuable treatment option against different cancers, strategies improve its potency and decrease the side effects associated with this have become increasingly relevant. Herein, we report an alternative CAR design that incorporates transmembrane domains ability recruit endogenous signaling molecules, eliminating need for stimulatory signals within structure. These molecule activating (ESMA) CARs triggered...
Due to the paucity of targetable antigens, triple-negative breast cancer (TNBC) remains a challenging subtype treat. In this study, we developed and evaluated chimeric antigen receptor (CAR) T cell-based treatment modality for TNBC by targeting stage-specific embryonic 4 (SSEA-4), glycolipid whose overexpression in has been correlated with metastasis chemoresistance. To delineate optimal CAR configuration, panel SSEA-4-specific CARs containing alternative extracellular spacer domains was...
The generation and expansion of functionally competent NK cells in vitro is great interest for their application immunotherapy cancer. Since CD33 constitutes a promising target myeloid malignancies, expressing CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR could not be efficiently expanded due to fratricide-like process which killed other had upregulated culture. This upregulation was dependent on the stimulation protocol encompassed up 50%...
CAR T cell research in solid tumors often lacks spatiotemporal information and therefore, there is a need for molecular tomography to facilitate high-throughput preclinical monitoring of cells.Furthermore, gap exists between macro-and microlevel imaging data better assess intratumor infiltration therapeutic cells.We addressed this challenge by combining 3D µComputer bioluminescence (µCT/BLT), light-sheet fluorescence microscopy (LSFM) cyclic immunofluorescence (IF) staining.Methods: NSG mice...
Carbohydrate markers of immature cells during prenatal human development can be aberrantly expressed in cancers and deserve evaluation as immune targets. A candidate target Ewing sarcoma is the globo-series ganglioside stage-specific embryonic antigen-4 (SSEA-4). We detected SSEA-4 expression on cell surface all 14 EwS lines 21 31 (68%) primary tumor biopsies. Among paired subpopulations with low versus high expression, SSEA-4high was significantly consistently associated functional...
Owing to their capacity eradicate tumors, T cells represent an attractive means for immunomodulation in cancer immunotherapy. In this context, chimeric antigen receptor (CAR) - based therapies are receiving increasing attention. The combination of antibody-derived specificity with cell effector function renders the immune MHC-independent and even enables targeting antigens which there is immunological tolerance. cells, genetically modified CAR, have shown impressive success treatment...
Clinical application of CD33-CAR-T cells remains challenging due to potential side effects and its restriction autologous products. We report on the generation primary CD33-CAR-NK cells, which are highly effective in combating AML vitro xenograft models. Transgene integration by BaEV-LV resulted 35-60% CAR-expression displayed unimpeded ex vivo-expansion as well increased cytotoxicity against CD33+ OCI-AML2 compared untransduced (UTD)-NK vitro. Using an NSG-SGM3 mouse model (n=7/group) a...
Abstract Cancers can aberrantly express carbohydrate antigens restricted to immature cells during prenatal human development, and these may be exploited for selective immune targeting. We studied expression functional associations of the globo-series ganglioside stage-specific embryonic antigen 4 (SSEA4), a cell surface marker stem cells, in Ewing sarcoma (EwS). Flow cytometry revealed SSEA4 on each 13 EwS lines, with moderate high densities 6 (46%) lines. Of 31 primary tumor biopsies, 21...
Abstract Cytokine-engineering is a promising strategy to overcome limitations of CAR T cell therapy in solid tumors. We have developed novel investigational medicinal product, consisting cells directed against ganglioside GD2 along with CAR-inducible secretion IL-18, enforce their activation response and effector functions the microenvironment cancers. Our lentiviral all-in-one vector combines constitutive expression 14.G2a antibody-derived GD2-specific, 4-1BB-costimulated inducible nuclear...
<p>Supplementary Materials and Methods</p>
<p>GD2 expression in cell lines after genome editing</p>
<p>Absolute numbers of T cells and IL-18 concentrations during manufacturing</p>
<p>Absolute numbers of T cells and IL-18 concentrations during manufacturing</p>
<p>GD2IL18CART tolerability experiment</p>
<p>Supplementary Materials and Methods</p>
<p>Dose-dependence of xenogeneic GvHD in mice receiving GD2IL18CART</p>
<p>Bioluminescence images 14 days after injection of luciferasetransduced CHLA-255 tumor cells</p>
<p>GD2 expression in cell lines after genome editing</p>