FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912170357> ?p ?o ?g. }

• W2912170357 endingPage "S218" @default.
• W2912170357 startingPage "S217" @default.
• W2912170357 abstract "The majority of bone marrow transplants (BMT) utilize granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood (mPB) as the source of hematopoietic stem cells (HSCs). However, CD34+ harvest with G-CSF is variable and frequently unpredictable, often requires multiple apheresis sessions and is associated with significant side effects. Identification of a mobilizing regimen that consistently produces high numbers of engraftable CD34+ cells without the need for G-CSF would be ideal. We previously reported that MGTA-145, a CXCR2 agonist, when combined with the CXCR4 inhibitor, plerixafor, rapidly mobilizes CD34+ cells (Blood 2017 130:1920). In the current study, we evaluated the ability of MGTA-145 plus plerixafor to mobilize and effectively engraft HSCs in a pre-clinical nonhuman primate (NHP) stem cell transplantation animal model. Rhesus macaques were mobilized with a single dose of MGTA-145, plerixafor or MGTA-145 plus plerixafor versus a multi-dose regimen of G-CSF. Detailed immune profiling was performed at 0 through 24 hours post treatment. Within 4 hours of dosing, MGTA-145 plus plerixafor resulted in a 16-fold increase in the number of CD34+CD90+CD45RA- HSCs in the periphery (p=0.0003, n=11), which were previously shown to predict successful transplant as evidenced by rapid neutrophil and platelet recovery in an autologous NHP transplant model (Sci Trans Med 2017 9:1145). Next, NHPs mobilized with MGTA-145 plus plerixafor were leukapheresed and CD34+ cells enriched by positive selection. These cells were genetically modified and transplanted back into the same NHP conditioned with 1080 cGy (4 doses over 48 hours). A representative apheresis yield was 2.3 × 106 CD34+ and 0.9 × 106 HSCs per kg, and the final dose of gene-marked CD34+ and HSCs for transplant following 48 hours in culture was 1.7 × 106 and 0.8 × 106 per kg, respectively. GFP marking in vivo was consistent with the marking on the primitive HSCs prior to transplant. Neutrophil and platelet engraftment occurred at day 10 and 15 post-transplant, respectively (Figure 1). The study is ongoing, and additional follow-up data on all available animals will be presented. Co-administration of MGTA-145 plus plerixafor leads to both rapid and efficacious mobilization of CD34+ cells in the pre-clinical NHP large animal model. We found that MGTA-145 plus plerixafor mobilized grafts contain large numbers of CD34+CD90+CD45RA- HSCs, which are capable of long-term multilineage reconstitution, and preliminary results from autologous transplantation studies in NHPs demonstrate that MGTA-145 plus plerixafor mobilized HSCs lead to rapid neutrophil and platelet recovery. This study demonstrates, for the first time, that CD34+ cells mobilized with a novel regimen of MGTA-145 plus plerixafor can be collected via leukapheresis, subsequently gene modified and transplanted into NHPs, resulting in rapid engraftment. The majority of bone marrow transplants (BMT) utilize granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood (mPB) as the source of hematopoietic stem cells (HSCs). However, CD34+ harvest with G-CSF is variable and frequently unpredictable, often requires multiple apheresis sessions and is associated with significant side effects. Identification of a mobilizing regimen that consistently produces high numbers of engraftable CD34+ cells without the need for G-CSF would be ideal. We previously reported that MGTA-145, a CXCR2 agonist, when combined with the CXCR4 inhibitor, plerixafor, rapidly mobilizes CD34+ cells (Blood 2017 130:1920). In the current study, we evaluated the ability of MGTA-145 plus plerixafor to mobilize and effectively engraft HSCs in a pre-clinical nonhuman primate (NHP) stem cell transplantation animal model. Rhesus macaques were mobilized with a single dose of MGTA-145, plerixafor or MGTA-145 plus plerixafor versus a multi-dose regimen of G-CSF. Detailed immune profiling was performed at 0 through 24 hours post treatment. Within 4 hours of dosing, MGTA-145 plus plerixafor resulted in a 16-fold increase in the number of CD34+CD90+CD45RA- HSCs in the periphery (p=0.0003, n=11), which were previously shown to predict successful transplant as evidenced by rapid neutrophil and platelet recovery in an autologous NHP transplant model (Sci Trans Med 2017 9:1145). Next, NHPs mobilized with MGTA-145 plus plerixafor were leukapheresed and CD34+ cells enriched by positive selection. These cells were genetically modified and transplanted back into the same NHP conditioned with 1080 cGy (4 doses over 48 hours). A representative apheresis yield was 2.3 × 106 CD34+ and 0.9 × 106 HSCs per kg, and the final dose of gene-marked CD34+ and HSCs for transplant following 48 hours in culture was 1.7 × 106 and 0.8 × 106 per kg, respectively. GFP marking in vivo was consistent with the marking on the primitive HSCs prior to transplant. Neutrophil and platelet engraftment occurred at day 10 and 15 post-transplant, respectively (Figure 1). The study is ongoing, and additional follow-up data on all available animals will be presented. Co-administration of MGTA-145 plus plerixafor leads to both rapid and efficacious mobilization of CD34+ cells in the pre-clinical NHP large animal model. We found that MGTA-145 plus plerixafor mobilized grafts contain large numbers of CD34+CD90+CD45RA- HSCs, which are capable of long-term multilineage reconstitution, and preliminary results from autologous transplantation studies in NHPs demonstrate that MGTA-145 plus plerixafor mobilized HSCs lead to rapid neutrophil and platelet recovery. This study demonstrates, for the first time, that CD34+ cells mobilized with a novel regimen of MGTA-145 plus plerixafor can be collected via leukapheresis, subsequently gene modified and transplanted into NHPs, resulting in rapid engraftment. Figure 1." @default.
• W2912170357 created "2019-02-21" @default.
• W2912170357 creator A5002264328 @default.
• W2912170357 creator A5037078524 @default.
• W2912170357 creator A5040518837 @default.
• W2912170357 creator A5047833836 @default.
• W2912170357 creator A5058498730 @default.
• W2912170357 creator A5060993908 @default.
• W2912170357 creator A5077686993 @default.
• W2912170357 creator A5090936468 @default.
• W2912170357 date "2019-03-01" @default.
• W2912170357 modified "2023-10-02" @default.
• W2912170357 title "Mgta-145 in Combination with Plerixafor Mobilizes Large Numbers of Hematopoietic Stem Cells That Lead to Rapid Engraftment Following Autologous Transplantation in Nonhuman Primates" @default.
• W2912170357 doi "https://doi.org/10.1016/j.bbmt.2018.12.298" @default.
• W2912170357 hasPublicationYear "2019" @default.
• W2912170357 type Work @default.
• W2912170357 sameAs 2912170357 @default.
• W2912170357 citedByCount "0" @default.
• W2912170357 crossrefType "journal-article" @default.
• W2912170357 hasAuthorship W2912170357A5002264328 @default.
• W2912170357 hasAuthorship W2912170357A5037078524 @default.
• W2912170357 hasAuthorship W2912170357A5040518837 @default.
• W2912170357 hasAuthorship W2912170357A5047833836 @default.
• W2912170357 hasAuthorship W2912170357A5058498730 @default.
• W2912170357 hasAuthorship W2912170357A5060993908 @default.
• W2912170357 hasAuthorship W2912170357A5077686993 @default.
• W2912170357 hasAuthorship W2912170357A5090936468 @default.
• W2912170357 hasBestOaLocation W29121703571 @default.
• W2912170357 hasConcept C109159458 @default.
• W2912170357 hasConcept C126322002 @default.
• W2912170357 hasConcept C129470790 @default.
• W2912170357 hasConcept C13373296 @default.
• W2912170357 hasConcept C203014093 @default.
• W2912170357 hasConcept C2776694085 @default.
• W2912170357 hasConcept C2777408962 @default.
• W2912170357 hasConcept C2777767877 @default.
• W2912170357 hasConcept C2778828106 @default.
• W2912170357 hasConcept C2781413609 @default.
• W2912170357 hasConcept C28328180 @default.
• W2912170357 hasConcept C2911091166 @default.
• W2912170357 hasConcept C71924100 @default.
• W2912170357 hasConcept C86803240 @default.
• W2912170357 hasConcept C8891405 @default.
• W2912170357 hasConcept C95444343 @default.
• W2912170357 hasConcept C98274493 @default.
• W2912170357 hasConceptScore W2912170357C109159458 @default.
• W2912170357 hasConceptScore W2912170357C126322002 @default.
• W2912170357 hasConceptScore W2912170357C129470790 @default.
• W2912170357 hasConceptScore W2912170357C13373296 @default.
• W2912170357 hasConceptScore W2912170357C203014093 @default.
• W2912170357 hasConceptScore W2912170357C2776694085 @default.
• W2912170357 hasConceptScore W2912170357C2777408962 @default.
• W2912170357 hasConceptScore W2912170357C2777767877 @default.
• W2912170357 hasConceptScore W2912170357C2778828106 @default.
• W2912170357 hasConceptScore W2912170357C2781413609 @default.
• W2912170357 hasConceptScore W2912170357C28328180 @default.
• W2912170357 hasConceptScore W2912170357C2911091166 @default.
• W2912170357 hasConceptScore W2912170357C71924100 @default.
• W2912170357 hasConceptScore W2912170357C86803240 @default.
• W2912170357 hasConceptScore W2912170357C8891405 @default.
• W2912170357 hasConceptScore W2912170357C95444343 @default.
• W2912170357 hasConceptScore W2912170357C98274493 @default.
• W2912170357 hasIssue "3" @default.
• W2912170357 hasLocation W29121703571 @default.
• W2912170357 hasOpenAccess W2912170357 @default.
• W2912170357 hasPrimaryLocation W29121703571 @default.
• W2912170357 hasRelatedWork W1863164085 @default.
• W2912170357 hasRelatedWork W1980069749 @default.
• W2912170357 hasRelatedWork W1998234776 @default.
• W2912170357 hasRelatedWork W2061394056 @default.
• W2912170357 hasRelatedWork W2113899987 @default.
• W2912170357 hasRelatedWork W2124119706 @default.
• W2912170357 hasRelatedWork W2127678757 @default.
• W2912170357 hasRelatedWork W2158093070 @default.
• W2912170357 hasRelatedWork W2386230525 @default.
• W2912170357 hasRelatedWork W2967245375 @default.
• W2912170357 hasVolume "25" @default.
• W2912170357 isParatext "false" @default.
• W2912170357 isRetracted "false" @default.
• W2912170357 magId "2912170357" @default.
• W2912170357 workType "article" @default.