Low-energy electron irradiation as a potent alternative to gamma irradiation for the inactivation of (CAR-)NK-92 cells in ATMP manufacturing
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ABSTRACT:
PROVIDER: PRJNA702504 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13733751_1.fastq.gz | Fastqsanger.gz | |||
| SRR13733751_2.fastq.gz | Fastqsanger.gz | |||
| SRR13733752_1.fastq.gz | Fastqsanger.gz | |||
| SRR13733752_2.fastq.gz | Fastqsanger.gz | |||
| SRR13733753_1.fastq.gz | Fastqsanger.gz |
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Project description:NK-92 cells and their CAR-modified derivatives exhibit strong cytotoxic activity against tumors and are promising "off-the-shelf" therapeutics compared to CAR-T cells. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cells need to be inactivated before transfusion. With increasing clinical use, there is a growing demand for enhanced safety and an efficient method that stops cell proliferation, but better maintains the cytotoxic effector functions of the cells compared to commonly used gamma irradiation. Recently, low-energy electron irradiation (LEEI) was successfully applied for inactivation of bacteria and viruses for vaccine production, and was described as a method for NK-92 inactivation for the first time. In the present publication, data on extensive characterization of LEEI and its comparison with gamma irradiation for the inactivation of parental NK-92 cells as well as CD123-directed CAR-NK-92 cells are provided. Our results show that both irradiation methods cause a progressive decrease in cell viability and are therefore suitable for inhibition of proliferation. Notably, cytotoxicity of the NK cells was significantly reduced by gamma irradiation, but not by LEEI three days after irradiation, compared to non-irradiated cells. Both gamma irradiation as well as LEEI led to substantial DNA-damage and an accumulation of irradiated cells in the G2/M phase. In addition, transcriptomic analysis of cells irradiated with both methods revealed approximately 12-fold more differentially expressed genes after gamma irradiation compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in CD56 expression but no changes in the levels of the activating receptors NKp46, NKG2D, and NKp30. Conclusions: The present data show that LEEI efficiently inactivates (CAR )NK-92 cells and sustains their cytotoxic capacity better than gamma irradiation. Taking into account additional logistic advantages of LEEI proves a potent alternative in the manufacturing of (CAR-)NK-92 cells for clinical application.
2021-05-17 | GSE166976 | GEO
Project description:BackgroundWith increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these "off-the-shelf" therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation. Recently, we showed proof of concept that low energy electron irradiation (LEEI) is a new method for NK-92 inactivation. LEEI has several advantages over gamma irradiation, including a faster reaction time, a more reproducible dose rate and much less requirements on radiation shielding. Here, LEEI was further evaluated as a promising alternative to gamma irradiation yielding cells with highly maintained cytotoxic effector function.MethodsEffectiveness and efficiency of LEEI and gamma irradiation were analyzed using NK-92 and CD123-directed CAR-NK-92 cells. LEE-irradiated cells were extensively characterized and compared to gamma-irradiated cells via flow cytometry, cytotoxicity assays, and comet assays, amongst others.ResultsOur results show that both irradiation methods caused a progressive decrease in cell viability and are, therefore, suitable for inhibition of cell proliferation. Notably, the NK-mediated specific lysis of tumor cells was maintained at stable levels for three days post-irradiation, with a trend towards higher activities after LEEI treatment as compared to gamma irradiation. Both gamma irradiation as well as LEEI led to substantial DNA damage and an accumulation of irradiated cells in the G2/M cell cycle phases. In addition, transcriptomic analysis of irradiated cells revealed approximately 12-fold more differentially expressed genes two hours after gamma irradiation, compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in surface expression of CD56, but no changes in the levels of the activating receptors NKp46, NKG2D, or NKp30.ConclusionsThe presented data show that LEEI inactivates (CAR-)NK-92 cells as efficiently as gamma irradiation, but with less impact on the overall gene expression. Due to logistic advantages, LEEI might provide a superior alternative for the manufacture of (CAR-)NK-92 cells for clinical application.
| S-EPMC8212864 | biostudies-literature
Project description:Analysis of gene expression in skin of rats subjected to electron irradiation and the effect of vitamin A supplements.
2007-10-10 | E-GEOD-284 | biostudies-arrayexpress
Project description:Analysis of gene expression in skin of rats subjected to electron irradiation and the effect of vitamin A supplements. Keywords: other
2003-03-20 | GSE284 | GEO
Project description:Radiation therapy (RT) remains a vital component of the curative multimodality therapy for many types of cancer including breast cancer (BC) disease. Thus, many efforts from research teams are needed to help clinicians in understanding the molecular portrait of a specific cancer type. Moreover, technological advances in RT are evolving with the use of hadrons, such as protons. However, cell and molecular changes induced by proton exposure are poorly characterized as well as molecular differences induced by high and low Linear Energy Transfer (LET) irradiation modalities, representing a topic of radiobiological interest. We analyze and compare molecular responses, in term of gene expression profile (GEP) changes, induced by conventional and non conventional radiation treatment modalities characterized by different LET values (using electron and proton beams respectively), delivering the same dose of IR, in tumorigenic and non-tumorigenic breast cell lines. We trust that this study could have a role in driving RT towards personalised treatments, evaluating possible combined treatments, based also on the molecular characterization in BC.
2018-12-26 | GSE103472 | GEO
Project description:The gene expression changes induced upon electron radiation in cancer cells is largely unexplored. We investigated the effect of electron radiation generated from 8 MeV Microtron in Daltons lymphoma ascites (DLA) cells bearing mice model. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. 48 Hours after irradiation, tumor cells were harvested from peritoneal cavity of both treatment-naive and total body irradiated mice. Microarray based genome-wide mRNA profiling approach was used to identify the differentially expressed genes between control and treated groups. 249 genes were found altered in DLA cells upon electron irradiation, of which 176 genes were upregulated and 73 genes were downregulated. The microarray results from this study were validated using reverse transcriptase PCR (RT-PCR) for selected candidate genes. In summary, total body irradiation with 8 MeV electrons has potential to inhibit the tumor cell proliferationin in vivo lymphoma model with the changes in specific signaling pathways and gene expression.
2013-03-05 | GSE44908 | GEO
Project description:The gene expression changes induced upon electron radiation in cancer cells is largely unexplored. We investigated the effect of electron radiation generated from 8 MeV Microtron in Daltons lymphoma ascites (DLA) cells bearing mice model. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. 48 Hours after irradiation, tumor cells were harvested from peritoneal cavity of both treatment-naive and total body irradiated mice. Microarray based genome-wide mRNA profiling approach was used to identify the differentially expressed genes between control and treated groups. 249 genes were found altered in DLA cells upon electron irradiation, of which 176 genes were upregulated and 73 genes were downregulated. The microarray results from this study were validated using reverse transcriptase PCR (RT-PCR) for selected candidate genes. In summary, total body irradiation with 8 MeV electrons has potential to inhibit the tumor cell proliferationin in vivo lymphoma model with the changes in specific signaling pathways and gene expression. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. Total RNA was isolated from DLA cells retrieved from control (treatment-naive) and irradiated mice (2 Gy) at 48 hours after radiation exposure.
2013-03-05 | E-GEOD-44908 | biostudies-arrayexpress
Project description:Electron beam irradiation is an efficient cold sterilization technique that has been widely utilized in food preservation. To understand the biological and morphological changes of microorganisms by electron beam irradiation, the D10 value, growth curve, and morphological characterization by scanning electron microscope (SEM) of Staphylococcus aureus were studied. Furthermore, Tandem mass tag (TMT)-based quantitative proteomic was performed to investigate the responses of Staphylococcus aureus to electron beam. The results showed that electron beam sensitized the irradiated strain and prolonged the lag phase of bacterial growth. There were 53, 96, 1055, and 431 differentially expressed proteins (DEPs) detected in 1-kGy irradiated strain (0 h-1-kGy), 2-kGy irradiated strain (0 h-2-kGy), 1-kGy irradiated strain after 24 h cultivation (24 h-1-kGy), and 2-kGy irradiated strain after 24 h cultivation (24 h-2-kGy) groups compared to unirradiated strain (control) group, respectively. Most of DEPs involved in DNA repair were found to be up-regulated. However, DEPs involved in biofilm formation and staphylococcal enterotoxin production were down-regulated. There were no noticeable morphological changes observed in irradiated S. aureus. These findings provided valuable information in the responses of S. aureus to electron beam irradiation, leading to a better understanding of the effects of electron beam irradiation on food pathogens.
2023-03-31 | PXD041285 |