FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2907986312> ?p ?o ?g. }

• W2907986312 endingPage "195" @default.
• W2907986312 startingPage "195" @default.
• W2907986312 abstract "Abstract Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). NK cell recognition of allogeneic tumors is strictly regulated by inhibitory killer cell immunoglobulin-like receptors (KIR) that bind to groups of HLA class I alleles. However, KIR expression on NK cells is highly diverse due to variation in gene content, polymorphism and copy number in combination with stochastic expression of the protein in individual cells. As a consequence, the number of efficacious allogeneic NK cells within a product isolated and expanded from random donors can vary a great deal and potentially be negligible. Our group has defined a repertoire of NK cells that is uniquely found in individuals with prior exposure to cytomegalovirus (CMV). Interestingly, these cells were shown to share many attributes usually reserved for adaptive immune cells including increased longevity, memory, and serial killing. We have previously described a 14-day protocol to enrich for adaptive NKG2C+CD57+ NK cells from CMV sero-positive donors with a homogenous expression of one single self-HLA specific KIR (self KIR). Here, we present new data on the GMP-transfer and clinical scale-up of this protocol, providing a route to off-the-shelf adaptive NK cell therapy for refractory high-risk AML/MDS. By screening >250 healthy donors, we first established the prerequisites for robust expansion of adaptive NK cells from peripheral blood of CMV+ donors and found that donors with >15% pre-existing adaptive NK cells showed efficient expansion of adaptive NK cells (Figure 1A-B). Apheresis products from a pool of pre-screened third-party donors are currently being collected for GMP freezing and use in an off-the-shelf setting intended for HLA mismatched patients to maximize alloreactivity by missing self. The GMP compatible protocol led to a robust expansion of clinical doses of self-KIR+ adaptive NK cells, with an average frequency of 60% self-specific KIR+ cells in the end product (Figure 1C-D). Based on the expression of self-KIR the expanded cells were educated, showing large dense-core granules and high levels of granzyme B. Further characterization in CyTOF using 36 phenotypic and functional markers revealed a highly activated state with high expression of DNAM-1 and CD2, which are critical for NK cell adhesion and function (Figure 1E). Notably, the expanded adaptive NK cells were negative for the HLA-E binding inhibitory receptor NKG2A, which is a major check point for T- and NK-cell based therapies. A microchip single-cell imaging platform revealed high serial killing capacity of the expanded adaptive NK cells. In flow cytometry-based killing assays and long-term killing assays this enhanced capacity for serial killing correlated with highly efficient targeting of mismatched PHA blasts (Figure 1F), tumor cell lines (Figure 1G), and MDS blasts. These pre-clinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing self-recognition as it was originally defined over thirty years ago. Disclosures Valamehr: Fate Therapeutics Inc.: Employment. Alici:Vycellix: Consultancy, Equity Ownership, Patents & Royalties, Research Funding; Intellia: Membership on an entity's Board of Directors or advisory committees. Ljunggren:Fate Therapeutics: Patents & Royalties; Vycellix: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Malmberg:Fate Therapeutics Inc.: Consultancy, Research Funding." @default.
• W2907986312 created "2019-01-11" @default.
• W2907986312 creator A5000628111 @default.
• W2907986312 creator A5004342251 @default.
• W2907986312 creator A5021412783 @default.
• W2907986312 creator A5022484705 @default.
• W2907986312 creator A5027151969 @default.
• W2907986312 creator A5029469057 @default.
• W2907986312 creator A5030228832 @default.
• W2907986312 creator A5031248010 @default.
• W2907986312 creator A5036467935 @default.
• W2907986312 creator A5042539600 @default.
• W2907986312 creator A5045493438 @default.
• W2907986312 creator A5056730527 @default.
• W2907986312 creator A5061606756 @default.
• W2907986312 creator A5065586908 @default.
• W2907986312 creator A5070964738 @default.
• W2907986312 creator A5072700291 @default.
• W2907986312 creator A5075290210 @default.
• W2907986312 creator A5079140244 @default.
• W2907986312 creator A5082782805 @default.
• W2907986312 creator A5084167089 @default.
• W2907986312 creator A5091546357 @default.
• W2907986312 date "2018-11-29" @default.
• W2907986312 modified "2023-10-16" @default.
• W2907986312 title "Efficient Scale-up and Pre-Clinical Evaluation of NKG2C+ Adaptive NK Cell Expansion for Therapy Against High-Risk AML/MDS" @default.
• W2907986312 doi "https://doi.org/10.1182/blood-2018-195" @default.
• W2907986312 hasPublicationYear "2018" @default.
• W2907986312 type Work @default.
• W2907986312 sameAs 2907986312 @default.
• W2907986312 citedByCount "0" @default.
• W2907986312 crossrefType "journal-article" @default.
• W2907986312 hasAuthorship W2907986312A5000628111 @default.
• W2907986312 hasAuthorship W2907986312A5004342251 @default.
• W2907986312 hasAuthorship W2907986312A5021412783 @default.
• W2907986312 hasAuthorship W2907986312A5022484705 @default.
• W2907986312 hasAuthorship W2907986312A5027151969 @default.
• W2907986312 hasAuthorship W2907986312A5029469057 @default.
• W2907986312 hasAuthorship W2907986312A5030228832 @default.
• W2907986312 hasAuthorship W2907986312A5031248010 @default.
• W2907986312 hasAuthorship W2907986312A5036467935 @default.
• W2907986312 hasAuthorship W2907986312A5042539600 @default.
• W2907986312 hasAuthorship W2907986312A5045493438 @default.
• W2907986312 hasAuthorship W2907986312A5056730527 @default.
• W2907986312 hasAuthorship W2907986312A5061606756 @default.
• W2907986312 hasAuthorship W2907986312A5065586908 @default.
• W2907986312 hasAuthorship W2907986312A5070964738 @default.
• W2907986312 hasAuthorship W2907986312A5072700291 @default.
• W2907986312 hasAuthorship W2907986312A5075290210 @default.
• W2907986312 hasAuthorship W2907986312A5079140244 @default.
• W2907986312 hasAuthorship W2907986312A5082782805 @default.
• W2907986312 hasAuthorship W2907986312A5084167089 @default.
• W2907986312 hasAuthorship W2907986312A5091546357 @default.
• W2907986312 hasConcept C147483822 @default.
• W2907986312 hasConcept C154317977 @default.
• W2907986312 hasConcept C188280979 @default.
• W2907986312 hasConcept C193419808 @default.
• W2907986312 hasConcept C202751555 @default.
• W2907986312 hasConcept C203014093 @default.
• W2907986312 hasConcept C2778102761 @default.
• W2907986312 hasConcept C502942594 @default.
• W2907986312 hasConcept C55493867 @default.
• W2907986312 hasConcept C86803240 @default.
• W2907986312 hasConcept C8891405 @default.
• W2907986312 hasConceptScore W2907986312C147483822 @default.
• W2907986312 hasConceptScore W2907986312C154317977 @default.
• W2907986312 hasConceptScore W2907986312C188280979 @default.
• W2907986312 hasConceptScore W2907986312C193419808 @default.
• W2907986312 hasConceptScore W2907986312C202751555 @default.
• W2907986312 hasConceptScore W2907986312C203014093 @default.
• W2907986312 hasConceptScore W2907986312C2778102761 @default.
• W2907986312 hasConceptScore W2907986312C502942594 @default.
• W2907986312 hasConceptScore W2907986312C55493867 @default.
• W2907986312 hasConceptScore W2907986312C86803240 @default.
• W2907986312 hasConceptScore W2907986312C8891405 @default.
• W2907986312 hasIssue "Supplement 1" @default.
• W2907986312 hasLocation W29079863121 @default.
• W2907986312 hasOpenAccess W2907986312 @default.
• W2907986312 hasPrimaryLocation W29079863121 @default.
• W2907986312 hasRelatedWork W2031253481 @default.
• W2907986312 hasRelatedWork W2090477263 @default.
• W2907986312 hasRelatedWork W2141330728 @default.
• W2907986312 hasRelatedWork W2164219360 @default.
• W2907986312 hasRelatedWork W2766647135 @default.
• W2907986312 hasRelatedWork W2946615038 @default.
• W2907986312 hasRelatedWork W3028899863 @default.
• W2907986312 hasRelatedWork W3031921507 @default.
• W2907986312 hasRelatedWork W4307373393 @default.
• W2907986312 hasRelatedWork W573847062 @default.
• W2907986312 hasVolume "132" @default.
• W2907986312 isParatext "false" @default.
• W2907986312 isRetracted "false" @default.
• W2907986312 magId "2907986312" @default.
• W2907986312 workType "article" @default.