Matches in SemOpenAlex for { <https://semopenalex.org/work/W2510173193> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W2510173193 abstract "Aim CD4 + CD127 − CD25 + FOXP3 + Regulatory T cells (Tregs) are shown to be enhanced in tolerant transplant patients and after ex vivo expansion to prolong graft survival in animal models without immunosuppression. Therefore, a number of centers have initiated clinical trials with expanded Tregs. The purpose of the present study was to further optimize the ex vivo expansion conditions and to characterize the expanded Tregs so as to transfer the technology to the clinic. Methods and results B cells to be used as stimulators in Treg cultures were expanded from the peripheral blood mononuclear cells (PBMC) of healthy “donors” using multimeric CD40L (Ultra-CD40L) ( n = 12). The resultant B cells expanded up to 1000 fold by day 14 and displayed increased expression of CD80, CD86, and HLA-DR, the hallmark of mature APC. These expanded “donor” B cells, were irradiated and used to stimulate purified CD4 + CD127 − CD25 + Tregs isolated from PBMC of an allogeneic volunteer (“recipient”) under Treg-promoting conditions with exogenous IL-2 and sirolimus (SRL). Initial cultures were for 28 days with weekly antigenic restimulations. The Tregs expanded up to 13-fold when SRL was removed after 21 days ( n = 8) and up to 28-fold when SRL was removed after 14 days ( n = 4). In the final optimized protocol, the Tregs were stimulated “donor”-specifically on days 0 and 7 and then polyclonally with anti-CD3/CD28 on day 14 without SRL, and were harvested on day 21 ( n = 3). This resulted in fold expansion into the thousands, as only + CD127 − CD25 + phenotype with >60% being FOXP3 + . More importantly, they inhibited MLRs of autologous responders in an antigen-specific manner ( p n = 8). These Tregs also demonstrated antigen-specific infectious tolerance by generating new Tregs in CFSE-labeled autologous responder cells cultured with the specific allostimulator ( n = 6). Conclusions We have optimized the protocol for ex vivo expansion of potent “donor”-specific Tregs. Therefore, after further scale-up in the cGMP and obtaining an IND from the FDA, we will be ready to utilize such Tregs clinically to induce transplant tolerance. R.S. Kornbluth: Other (Identify); Company/Organization; President and Chief Scientific Officer; Multimeric Biotherapeutics Inc. J.R. Leventhal: Other (Identify); Company/Organization; Co-Founder; TRACT Therapeutics, Inc." @default.
- W2510173193 created "2016-09-16" @default.
- W2510173193 creator A5010856093 @default.
- W2510173193 creator A5019264917 @default.
- W2510173193 creator A5040268724 @default.
- W2510173193 creator A5041221134 @default.
- W2510173193 creator A5041475657 @default.
- W2510173193 creator A5047335946 @default.
- W2510173193 creator A5060088724 @default.
- W2510173193 creator A5079079894 @default.
- W2510173193 creator A5081173252 @default.
- W2510173193 date "2016-09-01" @default.
- W2510173193 modified "2023-09-30" @default.
- W2510173193 title "P038 “Donor”-specific regulatory T cells for clinical transplant tolerance: Optimization of ex vivo expansion and characterization" @default.
- W2510173193 doi "https://doi.org/10.1016/j.humimm.2016.07.103" @default.
- W2510173193 hasPublicationYear "2016" @default.
- W2510173193 type Work @default.
- W2510173193 sameAs 2510173193 @default.
- W2510173193 citedByCount "0" @default.
- W2510173193 crossrefType "journal-article" @default.
- W2510173193 hasAuthorship W2510173193A5010856093 @default.
- W2510173193 hasAuthorship W2510173193A5019264917 @default.
- W2510173193 hasAuthorship W2510173193A5040268724 @default.
- W2510173193 hasAuthorship W2510173193A5041221134 @default.
- W2510173193 hasAuthorship W2510173193A5041475657 @default.
- W2510173193 hasAuthorship W2510173193A5047335946 @default.
- W2510173193 hasAuthorship W2510173193A5060088724 @default.
- W2510173193 hasAuthorship W2510173193A5079079894 @default.
- W2510173193 hasAuthorship W2510173193A5081173252 @default.
- W2510173193 hasConcept C123982805 @default.
- W2510173193 hasConcept C137061746 @default.
- W2510173193 hasConcept C150903083 @default.
- W2510173193 hasConcept C154317977 @default.
- W2510173193 hasConcept C16685009 @default.
- W2510173193 hasConcept C202751555 @default.
- W2510173193 hasConcept C203014093 @default.
- W2510173193 hasConcept C207001950 @default.
- W2510173193 hasConcept C26291073 @default.
- W2510173193 hasConcept C2776090121 @default.
- W2510173193 hasConcept C2778297628 @default.
- W2510173193 hasConcept C2779727006 @default.
- W2510173193 hasConcept C2781101188 @default.
- W2510173193 hasConcept C39347974 @default.
- W2510173193 hasConcept C55493867 @default.
- W2510173193 hasConcept C71924100 @default.
- W2510173193 hasConcept C79484868 @default.
- W2510173193 hasConcept C86803240 @default.
- W2510173193 hasConcept C8891405 @default.
- W2510173193 hasConceptScore W2510173193C123982805 @default.
- W2510173193 hasConceptScore W2510173193C137061746 @default.
- W2510173193 hasConceptScore W2510173193C150903083 @default.
- W2510173193 hasConceptScore W2510173193C154317977 @default.
- W2510173193 hasConceptScore W2510173193C16685009 @default.
- W2510173193 hasConceptScore W2510173193C202751555 @default.
- W2510173193 hasConceptScore W2510173193C203014093 @default.
- W2510173193 hasConceptScore W2510173193C207001950 @default.
- W2510173193 hasConceptScore W2510173193C26291073 @default.
- W2510173193 hasConceptScore W2510173193C2776090121 @default.
- W2510173193 hasConceptScore W2510173193C2778297628 @default.
- W2510173193 hasConceptScore W2510173193C2779727006 @default.
- W2510173193 hasConceptScore W2510173193C2781101188 @default.
- W2510173193 hasConceptScore W2510173193C39347974 @default.
- W2510173193 hasConceptScore W2510173193C55493867 @default.
- W2510173193 hasConceptScore W2510173193C71924100 @default.
- W2510173193 hasConceptScore W2510173193C79484868 @default.
- W2510173193 hasConceptScore W2510173193C86803240 @default.
- W2510173193 hasConceptScore W2510173193C8891405 @default.
- W2510173193 hasLocation W25101731931 @default.
- W2510173193 hasOpenAccess W2510173193 @default.
- W2510173193 hasPrimaryLocation W25101731931 @default.
- W2510173193 hasRelatedWork W2003429590 @default.
- W2510173193 hasRelatedWork W2024729349 @default.
- W2510173193 hasRelatedWork W2054280740 @default.
- W2510173193 hasRelatedWork W2058801231 @default.
- W2510173193 hasRelatedWork W2071040581 @default.
- W2510173193 hasRelatedWork W2075995574 @default.
- W2510173193 hasRelatedWork W2127281106 @default.
- W2510173193 hasRelatedWork W2226699294 @default.
- W2510173193 hasRelatedWork W2284337953 @default.
- W2510173193 hasRelatedWork W2505999275 @default.
- W2510173193 hasRelatedWork W2531065150 @default.
- W2510173193 hasRelatedWork W2549076422 @default.
- W2510173193 hasRelatedWork W2582975296 @default.
- W2510173193 hasRelatedWork W2583821351 @default.
- W2510173193 hasRelatedWork W2584081704 @default.
- W2510173193 hasRelatedWork W2781744086 @default.
- W2510173193 hasRelatedWork W2920665535 @default.
- W2510173193 hasRelatedWork W2981310382 @default.
- W2510173193 hasRelatedWork W3087550623 @default.
- W2510173193 hasRelatedWork W3158424044 @default.
- W2510173193 isParatext "false" @default.
- W2510173193 isRetracted "false" @default.
- W2510173193 magId "2510173193" @default.
- W2510173193 workType "article" @default.