Matches in SemOpenAlex for { <https://semopenalex.org/work/W43134640> ?p ?o ?g. }
Showing items 1 to 69 of
69
with 100 items per page.
- W43134640 abstract "Epstein Barr Virus driven post transplant lymphoproliferative disease (PTLD) is aserious complication following either stem cell or solid organ transplantation (SOT),occurring as a result of suppressed cellular immunity. Adoptive transfer of EBVspecific cytotoxic T cells (EBV-CTLs) is effective as both prophylaxis and treatmentfor PTLD following stem cell transplantation, but is less effective when applied toPTLD after SOT. It is likely that the continued pharmacologic immunosuppressiondesigned to prevent graft rejection compromises the function of infused EBV-CTLs.To address this issue, we have generated calcineurin (CN) mutants that do not bind theimmunosuppressants Tacrolimus (FK506) and Cyclosporin A (CsA), thereforeconferring resistance to these CN inhibitors. A panel of 54 such mutants was designed,generated and screened in a Luciferase expression assay, with identification of thosecapable of resisting suppression with FK506, CsA or both. Subsequently, in assaysutilising both the Jurkat T cell line and primary human EBV-CTL lines, mutant CNa12conferred resistance to CsA, mutant CNa22 conferred resistance to FK506 and mutantCNb30 rendered cells resistant to both calcineurin inhibitors. EBV-CTL linestransduced with a retroviral vector encoding these mutants retained the ability to bothproliferate and secrete normal levels of interferon-gamma in the presence of therapeutic andsupratherapeutic levels of FK506 (CNa12), CsA (CNa22), or both (CNb30). Thecytotoxicity, phenotype and antigen dependence of EBV-CTL lines were unaffectedby expression of mutant CN. A xenogenic murine model of PTLD was established inthe RAG2^{-/-}/gamma c^{-/-}/C5^{-/-} triple knockout SCID mouse strain and the ability of EBV-CTLlines to induce tumour regression was examined. Administration of EBV-CTLs causedregression of subcutaneous LCL tumours in vivo in some donors. This model will beutilised in further investigations of transduced EBV-CTLs in vivo. The generation ofEBV-CTLs that are resistant to CN inhibitors should allow effective immunotherapyin the SOT setting without risking rejection of the graft by reducingimmunosuppression. Additionally this represents a generic approach to improvingimmunotherapy in the face of immunosuppression in other settings." @default.
- W43134640 created "2016-06-24" @default.
- W43134640 creator A5020057105 @default.
- W43134640 date "2010-03-28" @default.
- W43134640 modified "2023-09-23" @default.
- W43134640 title "Generation of calcineurin inhibitorresistant EBV-CTLs for thetreatment of post transplantlymphoma" @default.
- W43134640 hasPublicationYear "2010" @default.
- W43134640 type Work @default.
- W43134640 sameAs 43134640 @default.
- W43134640 citedByCount "0" @default.
- W43134640 crossrefType "dissertation" @default.
- W43134640 hasAuthorship W43134640A5020057105 @default.
- W43134640 hasConcept C128057223 @default.
- W43134640 hasConcept C141071460 @default.
- W43134640 hasConcept C147969180 @default.
- W43134640 hasConcept C154317977 @default.
- W43134640 hasConcept C159047783 @default.
- W43134640 hasConcept C167672396 @default.
- W43134640 hasConcept C179464577 @default.
- W43134640 hasConcept C202751555 @default.
- W43134640 hasConcept C203014093 @default.
- W43134640 hasConcept C2776090121 @default.
- W43134640 hasConcept C2911091166 @default.
- W43134640 hasConcept C55493867 @default.
- W43134640 hasConcept C71924100 @default.
- W43134640 hasConcept C86803240 @default.
- W43134640 hasConcept C8891405 @default.
- W43134640 hasConceptScore W43134640C128057223 @default.
- W43134640 hasConceptScore W43134640C141071460 @default.
- W43134640 hasConceptScore W43134640C147969180 @default.
- W43134640 hasConceptScore W43134640C154317977 @default.
- W43134640 hasConceptScore W43134640C159047783 @default.
- W43134640 hasConceptScore W43134640C167672396 @default.
- W43134640 hasConceptScore W43134640C179464577 @default.
- W43134640 hasConceptScore W43134640C202751555 @default.
- W43134640 hasConceptScore W43134640C203014093 @default.
- W43134640 hasConceptScore W43134640C2776090121 @default.
- W43134640 hasConceptScore W43134640C2911091166 @default.
- W43134640 hasConceptScore W43134640C55493867 @default.
- W43134640 hasConceptScore W43134640C71924100 @default.
- W43134640 hasConceptScore W43134640C86803240 @default.
- W43134640 hasConceptScore W43134640C8891405 @default.
- W43134640 hasLocation W431346401 @default.
- W43134640 hasOpenAccess W43134640 @default.
- W43134640 hasPrimaryLocation W431346401 @default.
- W43134640 hasRelatedWork W1482291578 @default.
- W43134640 hasRelatedWork W1941024160 @default.
- W43134640 hasRelatedWork W1975401834 @default.
- W43134640 hasRelatedWork W1988176595 @default.
- W43134640 hasRelatedWork W2008323503 @default.
- W43134640 hasRelatedWork W2045323288 @default.
- W43134640 hasRelatedWork W2046828698 @default.
- W43134640 hasRelatedWork W2055958799 @default.
- W43134640 hasRelatedWork W2059530009 @default.
- W43134640 hasRelatedWork W2085814835 @default.
- W43134640 hasRelatedWork W2105079905 @default.
- W43134640 hasRelatedWork W2550427617 @default.
- W43134640 hasRelatedWork W2553571042 @default.
- W43134640 hasRelatedWork W2564469952 @default.
- W43134640 hasRelatedWork W2564485987 @default.
- W43134640 hasRelatedWork W2572558723 @default.
- W43134640 hasRelatedWork W2904020651 @default.
- W43134640 hasRelatedWork W3018802486 @default.
- W43134640 hasRelatedWork W3083913990 @default.
- W43134640 hasRelatedWork W800973367 @default.
- W43134640 isParatext "false" @default.
- W43134640 isRetracted "false" @default.
- W43134640 magId "43134640" @default.
- W43134640 workType "dissertation" @default.