Intermediate cryopreservation and transcriptomic profiling as strategy to identify optimal donors for functional NK cell expansion for AML immunotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE309309 | GEO | 2026/02/12
REPOSITORIES: GEO
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Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients Eight healthy donor and eight myeloma patients were used in the study. Non-expanded natural killer (NK) cells were isolated from PBMCs of healthy donors and myeloma patients. Expanded natural killer (ENK) cells were generated from same set of samples as mentioned in expansion protocol. All ENK and NK cells were used for gene expression profiling.
2011-03-08 | E-GEOD-27838 | biostudies-arrayexpress
Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients
2011-03-08 | GSE27838 | GEO
Project description:B-cell lymphoma/leukemia (BCL) 11B represents a major regulator of vital processes in post-thymic lymphocytes as well as of lymphocyte differentiation by blocking NK cell and promoting T cell development and is thus considered a \\"guardian of T cell fate\\". Interestingly, on the one hand, NK cell maturation correlates with increased expression of BCL11B, on the other hand, native or induced T cell populations characterized by multiple NK cell features showed reduced BCL11B expression. Both NK cells or T cells display unique and desired features for cellular therapies. NK cells are able to efficiently lyse cancerous or virally infected cells but can only be poorly expanded in vitro. In contrast, T cell cytotoxic activity is limited by T cell receptor (TCR) but in vitro expansion is easily achievable. We show that from buffy coats of healthy donors isolated and CRISPR/Cas9-mediated BCL11B knock-out CD8+ T cells stimulated with IL-15 acquired remarkable innate characteristics and combine spontaneous and antibody-dependent NK cell cytotoxicity with T cell capability for rapid in vitro expansion. The observed features of the induced innate CD8+ (iiT8) cells make them an interesting and promising tool for cellular therapy.
2022-12-07 | E-MTAB-12064 | biostudies-arrayexpress
Project description:Natural killer (NK) cells are innate lymphocytes that play a critical role in host defense against viral infection. In addition to rapid effector cytokine production and direct cytotoxicity, NK cells exhibit features of adaptive immunity, including the capacity to undergo robust antigen-specific clonal proliferation and to generate immunological memory. However, the transcriptional programs and regulators governing dynamic NK cell responses to viral infection have not been fully uncovered. In this study, we identified Transcription factor 19 (TCF19) as a key driver of NK cell proliferation and calcium signaling in the context of mouse cytomegalovirus infection. Ablation of TCF19 was detrimental to NK cell clonal expansion and host protection against viral infection. Tcf19-/- NK cells were also unable to properly mobilize calcium downstream of antigen signaling to mediate cytotoxicity. Altogether, we find that TCF19 drives a transcriptional program that coordinates the innate and adaptive NK cell responses against viral infection.
2025-06-23 | GSE265814 | GEO
Project description:Natural killer (NK) cells are innate lymphocytes that play a critical role in host defense against viral infection. In addition to rapid effector cytokine production and direct cytotoxicity, NK cells exhibit features of adaptive immunity, including the capacity to undergo robust antigen-specific clonal proliferation and to generate immunological memory. However, the transcriptional programs and regulators governing dynamic NK cell responses to viral infection have not been fully uncovered. In this study, we identified Transcription factor 19 (TCF19) as a key driver of NK cell proliferation and calcium signaling in the context of mouse cytomegalovirus infection. Ablation of TCF19 was detrimental to NK cell clonal expansion and host protection against viral infection. Tcf19-/- NK cells were also unable to properly mobilize calcium downstream of antigen signaling to mediate cytotoxicity. Altogether, we find that TCF19 drives a transcriptional program that coordinates the innate and adaptive NK cell responses against viral infection.
2025-06-23 | GSE281121 | GEO
Project description:Clinical Natural Killer (NK) cell therapy for the treatment of leukemia is currently limited by the availability of larger numbers of functional NK cells. In vitro NK cell expansion can be used to generate higher numbers of NK cells and shows the potential to improve the cytotoxicity against tumor cells. A critical need for the clinical application of manufactured NK cells is their molecular and functional characterization. In order to characterize primary and expanded NK cells of all donors the cells were analyzed on the surfaceome level by using CSC technology in combination with total gene expression analysis using whole human genome oligo microarrays.
2022-12-31 | GSE64812 | 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:Allogeneic natural killer (NK) cell therapies are a valuable treatment option for cancer, given their remarkable safety and favorable efficacy profile. Although the use of allogeneic donors allows for off-the-shelf and timely patient treatment, intrinsic interindividual differences put clinical efficacy at risk. The identification of donors with superior anti-tumor activity is essential to ensure the success of adoptive NK cell therapies. Here, we investigated the heterogeneity of 10 umbilical cord blood stem cell-derived NK cell batches. First, we evaluated the donors’ cytotoxic potential against tumor cell lines from solid and hematological cancer indications, to distinguish a group of superior, “excellent” killers (4/10), compared to “good” killers (6/10). Next, bulk and single-cell RNA-Sequencing, performed at different stages of NK differentiation, revealed distinct transcriptomic features of the two groups. Excellent donors showed an enrichment in cytotoxicity pathways and a depletion of myeloid traits, linked to the presence of a larger population of effector-like NK cells early on during differentiation. Consequently, we defined a multi-factorial gene expression signature able to predict the donors’ anti-tumor potential. Our study contributes to the identification of key traits of superior NK cell batches, supporting the development of efficacious NK therapeutics and the achievement of durable anti-tumor responses
2024-10-10 | GSE249991 | GEO
Project description:Allogeneic natural killer (NK) cell therapies are a valuable treatment option for cancer, given their remarkable safety and favorable efficacy profile. Although the use of allogeneic donors allows for off-the-shelf and timely patient treatment, intrinsic interindividual differences put clinical efficacy at risk. The identification of donors with superior anti-tumor activity is essential to ensure the success of adoptive NK cell therapies. Here, we investigated the heterogeneity of 10 umbilical cord blood stem cell-derived NK cell batches. First, we evaluated the donors’ cytotoxic potential against tumor cell lines from solid and hematological cancer indications, to distinguish a group of superior, “excellent” killers (4/10), compared to “good” killers (6/10). Next, bulk and single-cell RNA-Sequencing, performed at different stages of NK differentiation, revealed distinct transcriptomic features of the two groups. Excellent donors showed an enrichment in cytotoxicity pathways and a depletion of myeloid traits, linked to the presence of a larger population of effector-like NK cells early on during differentiation. Consequently, we defined a multi-factorial gene expression signature able to predict the donors’ anti-tumor potential. Our study contributes to the identification of key traits of superior NK cell batches, supporting the development of efficacious NK therapeutics and the achievement of durable anti-tumor responses
2024-10-10 | GSE249990 | GEO
Project description:We compared transcriptome of different types of NK cells including obtained from Umbilical Blood (UCB-NK) from 3 donors, both UCB56 NK cells that were isolated from the UCB unit as well as UCB34 NK cells that were differentiated from CD34+ cells, and derived from human iPSC (iPSC-NK), pre and post antigen presenting cell expansion. When comparing the similarity of the NK cells populations by the number of differentially expressed genes to iPSC NK cells, there were the pre and post expansion cells clustered together
2020-05-13 | GSE150363 | GEO