NK cell expansion on uAPC helper cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA682740 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13201953_1.fastq.gz | Fastqsanger.gz | |||
| SRR13201953_2.fastq.gz | Fastqsanger.gz | |||
| SRR13201954_1.fastq.gz | Fastqsanger.gz | |||
| SRR13201954_2.fastq.gz | Fastqsanger.gz | |||
| SRR13201955_1.fastq.gz | Fastqsanger.gz |
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Project description:Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK cells expressing chimeric antigen receptors (CARs) have enhanced effector function against various type of cancer and are attractive contenders for the next generation of cancer immunotherapies. However, a number of factors have hindered the application of NK cells for cellular therapy, including their poor in vitro growth kinetics and relatively low starting percentages within the mononuclear cell fraction of peripheral blood or cord blood (CB). To overcome these limitations, we genetically-engineered human leukocyte antigen (HLA)-A- and HLA-B- K562 cells to enforce the expression of CD48, 4-1BBL, and membrane-bound IL-21 (mbIL21), creating a universal antigen presenting cell (uAPC) capable of stimulating their cognate receptors on NK cells. We have shown that uAPC can drive the expansion of both non-transduced (NT) and CAR-transduced CB derived NK cells by greater than 900-fold in 2 weeks of co-culture with excellent purity (>99.9%) and without indications of senescence/exhaustion. We confirmed that uAPC-expanded research- and clinical-grade NT and CAR-transduced NK cells have higher metabolic fitness and display enhanced effector function against tumor targets compared to the corresponding cell fractions cultured without uAPCs. This novel approach allowed the expansion of highly pure GMP-grade CAR NK cells at optimal cell numbers to be used for adoptive CAR NK cell-based cancer immunotherapy.
2020-12-06 | GSE162716 | GEO
Project description:Ex vivo activation and expansion of natural killer (NK) cells is a strategy to produce sufficient numbers of these effector cells for adoptive immunotherapy. Therefore we aimed at the development of an automated, clinical scale NK cell expansion process and compared NK cells after manual and automated expansion.We found only a small subset of 124 genes that significantly varied between both sample groups. These genes were associated with movement of leukocytes were identified including a group of genes for NK cell movement (CMKLR1, CX3CR1, S1PR5, GNLY and CXCR1) which were slightly higher expressed after automated compared to manual expansion. Nevertheless, the expansion profiles of NK cells after automated or manual expansion were rather similar in comparison to the remarkable difference between primary and expanded NK cells in general represented by the vast majority of regulated genes between the analyzed sample groups. Pathway analysis revealed that most of regulated genes upon expansion were associated with cell cycle regulation, DNA replication, DNA recombination and DNA repair, regulation of apoptosis and cell survival as well as cytokine signaling. Furthermore, the expression of many NK cell relevant markers was changed upon expansion with the strongest effects on up regulation of TRAIL and FASL, inhibitory TIGIT and chemokine receptors CCR2, CCR5 and CXCR6. In addition, granzyme M was down regulated but other important effector molecules like TNFa, perforin and granzymes A, B and K were up regulated. In summary we could show that manual and automatically expanded NK cells show a similar expansion profile while the differ significantly from primary NK cells. Up regulation of many NK cell relevant markers indicate for an enhanced NK cell functionaility after ex vivo activation and expansion. 24 samples were analyzed in total. 6 biological replicates represented by cells from different donors. 4 different samples per donor: freshly isolated NK cells (d0) and NK cells expanded for 14 days under 3 different conditions: in co-culture with EBV-LCL feeder cells and 500 U/mL IL2 either cultivated manually in T75 flasks (T) or automatically using the CliniMACS Prodigy system (P); NK cells cultured with 500 U/ml IL2 without feeder cells (I)
2015-04-23 | E-GEOD-62654 | biostudies-arrayexpress
Project description:Natural Killer (NK) cells are innate lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. NK cells also expand and accumulate in affected tissues, but the role of NK cell expansion in tumor and viral control is not well understood. Here, we describe that post-transcriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion, without overtly affecting NK cell effector functions. HuR-dependent NK cell expansion facilitated control of solid tumors, but it was dispensable for control of tumor metastases. In virus infection, HuR-dependent NK cell expansion contributed to long-term viral control in the absence of adaptive immunity without affecting acute infection. HuR-deficient NK cells displayed defects in expression of and splicing in cell cycle-associated genes, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex that is involved in chromosome separation during cell division. Furthermore, we identified an essential role for SKA2 in NK cell expansion. These results show that post-transcriptional regulation by HuR specifically affects NK cell expansion which is required for control of several solid tumors and long-term virus infection.
2023-08-31 | GSE217392 | GEO
Project description:RNA-seq analysis of feeder cells for NK cells expansion
| PRJNA655693 | ENA
Project description:Ex vivo activation and expansion of natural killer (NK) cells is a strategy to produce sufficient numbers of these effector cells for adoptive immunotherapy. Therefore we aimed at the development of an automated, clinical scale NK cell expansion process and compared NK cells after manual and automated expansion.We found only a small subset of 124 genes that significantly varied between both sample groups. These genes were associated with movement of leukocytes were identified including a group of genes for NK cell movement (CMKLR1, CX3CR1, S1PR5, GNLY and CXCR1) which were slightly higher expressed after automated compared to manual expansion. Nevertheless, the expansion profiles of NK cells after automated or manual expansion were rather similar in comparison to the remarkable difference between primary and expanded NK cells in general represented by the vast majority of regulated genes between the analyzed sample groups. Pathway analysis revealed that most of regulated genes upon expansion were associated with cell cycle regulation, DNA replication, DNA recombination and DNA repair, regulation of apoptosis and cell survival as well as cytokine signaling. Furthermore, the expression of many NK cell relevant markers was changed upon expansion with the strongest effects on up regulation of TRAIL and FASL, inhibitory TIGIT and chemokine receptors CCR2, CCR5 and CXCR6. In addition, granzyme M was down regulated but other important effector molecules like TNFa, perforin and granzymes A, B and K were up regulated. In summary we could show that manual and automatically expanded NK cells show a similar expansion profile while the differ significantly from primary NK cells. Up regulation of many NK cell relevant markers indicate for an enhanced NK cell functionaility after ex vivo activation and expansion.
2015-04-23 | GSE62654 | GEO
Project description:Natural killer (NK) cells can be divided into phenotypic subsets based on the expression of receptors that bind self-MHC-I molecules with differing affinities; a concept termed licensing or education. Here we show that NK cell subsets exhibit markedly different migratory, effector, and immunoregulatory functions on dendritic cells and antigen-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells preferentially trafficked to draining lymph nodes and produced GM-CSF, which promoted the expansion and activation of dendritic cells, and ultimately resulted in sustained antigen-specific CD8+ T cell responses. In contrast, licensed NK cells preferentially migrated to infected parenchymal tissues and produced greater levels of interferon-γ (IFN-γ). Importantly, human NK cell subsets exhibited similar phenotypic characteristics and patterns of cytokine production. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset in inflamed tissues and the latter as modulators of adaptive immunity helping to prime immune responses in draining lymph nodes.
2017-08-22 | GSE72632 | GEO
Project description:Early T follicular helper cell activity accelerates HCV-specific B cell expansion
| PRJNA661324 | ENA
Project description:In order to gain a better understanding of gene expression during early malaria infection, we conducted microarray analysis of early blood responses in mice infected with erythrocytic stage Plasmodium chabaudi. Immediately following infection, we observed coordinated and sequential waves of immune responses, with interferon-associated gene transcripts dominating by 16 hours post-infection, followed by strong increases in natural killer (NK) cell-associated and MHC class I-related transcripts by 32 hours post-infection. We hypothesized that the observed elevation in NK cell-associated transcripts could be the result of a dramatic increase in the proportion of NK cells in the blood during infection, which we confirmed by flow cytometry. Subsequent microarray analysis of NK cells isolated from the peripheral blood of infected mice revealed a cell proliferation expression signature consistent with the observation that NK cells replicate in response to infection. Early proliferation of NK cells was directly observed in studies with adoptively transferred cells in infected mice. These data indicate that the early response to P. chabaudi infection of the blood is marked by a primary wave of interferon with a subsequent response by NK cells. Keywords: murine NK cell response to Plasmodium chabaudi infection We analyzed a series of 10 MEEBO arrays on which were hybed RNA amplified from NK cells of C57BL/6 mice either mock-infected or infected with P. chabaudi AS.
2010-05-19 | E-GEOD-12727 | biostudies-arrayexpress
Project description:Single-cell transcriptomics was performed to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis (n=19), during treatment (n=21) and at relapse (n=6). The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.
2023-07-18 | E-MTAB-13157 | biostudies-arrayexpress
Project description:Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. Natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed for the first time RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, and we observed that these decidual-like NK cells exhibited lower degranulation besides higher granzyme B and perforin expression than CD9- NK cells. These results provide new insights on the physiopathology of NK cells during their reconstitution after autoHSCT.
2022-10-26 | GSE199608 | GEO