{"id":{"repo_id":"ucl","oai_identifier":"oai:eprints.ucl.ac.uk.OAI2:15820"},"canonical_url":"https://search.dev.ndltd.org/etd/ucl/oai:eprints.ucl.ac.uk.OAI2:15820","repository":{"repo_id":"ucl","name":"University College London","base_url":"https://discovery.ucl.ac.uk/cgi/oai2"},"display":{"title":"Selective allodepletion to improve anti-viral and anti-leukaemic responses after haploidentical transplantation","abstract":"Immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical SCT, but infection and leukaemic relapse remain problematic. To develop a rational approach to refining allodepletion, we characterized the expression of surface markers and cytokines on proliferating alloreactive T-cells flow cytometrically. CD25 was expressed on 83 % of CFSE-dim alloreactive T-cells, confirming this as an excellent target for allodepletion. 70 % of the alloreactive CD25-ve population expressed CD71, identifying this as a novel marker to target alloreactive T-cells that persist after CD25 depletion. We compared residual alloreactivity to host or 3rd party after CD25 vs combined CD25/71 immunomagnetic depletion in 8 HLA-mismatched donor-recipient pairs. In 1o MLRs, residual responses to host were undetectable after CD25/71 depletion. In 2o MLRs, CD25/71 depletion resulted in significantly lower residual proliferative response to host than CD25 depletion (median 4.8% of the response of unmanipulated PBMC vs 9.9%, p < 0.01). Likewise, the median residual reactivity to host in IFN-γ ELISPOT assays was significantly lower after combined CD25/71 than CD25 allodepletion (14.1 % vs 54.6%, p < 0.05). Third party responses after CD25/71 allodepletion were equivalent to unmanipulated PBMCs in both assays. In pentamer and IFN-γ ELISPOT assays, anti-viral responses to CMV, EBV and adenovirus were preserved after combined CD25/71 allodepletion. Finally, we showed that CD25/71 allodepleted T-cells can be redirected to recognize and secrete IFN-γ and granzyme B in response to CD19 cell lines and primary ALL blasts through lentiviral transfer of a chimeric αCD19ζ TCR. This strategy may facilitate immunotherapy with larger doses of allodepleted T-cells after haplo-SCT, enhancing graft versus leukaemia and anti-viral effects.","abstract_html":"Immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical SCT, but infection and leukaemic relapse remain problematic. To develop a rational approach to refining allodepletion, we characterized the expression of surface markers and cytokines on proliferating alloreactive T-cells flow cytometrically. CD25 was expressed on 83 % of CFSE-dim alloreactive T-cells, confirming this as an excellent target for allodepletion. 70 % of the alloreactive CD25-ve population expressed CD71, identifying this as a novel marker to target alloreactive T-cells that persist after CD25 depletion. We compared residual alloreactivity to host or 3rd party after CD25 vs combined CD25/71 immunomagnetic depletion in 8 HLA-mismatched donor-recipient pairs. In 1o MLRs, residual responses to host were undetectable after CD25/71 depletion. In 2o MLRs, CD25/71 depletion resulted in significantly lower residual proliferative response to host than CD25 depletion (median 4.8% of the response of unmanipulated PBMC vs 9.9%, p &lt; 0.01). Likewise, the median residual reactivity to host in IFN-γ ELISPOT assays was significantly lower after combined CD25/71 than CD25 allodepletion (14.1 % vs 54.6%, p &lt; 0.05). Third party responses after CD25/71 allodepletion were equivalent to unmanipulated PBMCs in both assays. In pentamer and IFN-γ ELISPOT assays, anti-viral responses to CMV, EBV and adenovirus were preserved after combined CD25/71 allodepletion. Finally, we showed that CD25/71 allodepleted T-cells can be redirected to recognize and secrete IFN-γ and granzyme B in response to CD19 cell lines and primary ALL blasts through lentiviral transfer of a chimeric αCD19ζ TCR. This strategy may facilitate immunotherapy with larger doses of allodepleted T-cells after haplo-SCT, enhancing graft versus leukaemia and anti-viral effects.","abstract_has_math":false,"creators":["Samarasinghe, S."],"institution":"UCL (University College London)","degree_name":null,"degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-03","date_published":"2009-03","updated_at":"2026-07-24T05:10:54Z","subjects":["Molecular Immunology Unit"],"languages":["en","eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Samarasinghe, S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2009-03"]},{"key":"dc:date.issued","label":"Date","values":["2009-03"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Institute of Child Health"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["UCL (University College London)"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.ucl.ac.uk/id/eprint/15820/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Molecular Immunology Unit"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.ucl.ac.uk/id/eprint/15820/1/15820.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical SCT, but infection and leukaemic relapse remain problematic. To develop a rational approach to refining allodepletion, we characterized the expression of surface markers and cytokines on proliferating alloreactive T-cells flow cytometrically. CD25 was expressed on 83 % of CFSE-dim alloreactive T-cells, confirming this as an excellent target for allodepletion. 70 % of the alloreactive CD25-ve population expressed CD71, identifying this as a novel marker to target alloreactive T-cells that persist after CD25 depletion. We compared residual alloreactivity to host or 3rd party after CD25 vs combined CD25/71 immunomagnetic depletion in 8 HLA-mismatched donor-recipient pairs. In 1o MLRs, residual responses to host were undetectable after CD25/71 depletion. In 2o MLRs, CD25/71 depletion resulted in significantly lower residual proliferative response to host than CD25 depletion (median 4.8% of the response of unmanipulated PBMC vs 9.9%, p < 0.01). Likewise, the median residual reactivity to host in IFN-γ ELISPOT assays was significantly lower after combined CD25/71 than CD25 allodepletion (14.1 % vs 54.6%, p < 0.05). Third party responses after CD25/71 allodepletion were equivalent to unmanipulated PBMCs in both assays. In pentamer and IFN-γ ELISPOT assays, anti-viral responses to CMV, EBV and adenovirus were preserved after combined CD25/71 allodepletion. Finally, we showed that CD25/71 allodepleted T-cells can be redirected to recognize and secrete IFN-γ and granzyme B in response to CD19 cell lines and primary ALL blasts through lentiviral transfer of a chimeric αCD19ζ TCR. This strategy may facilitate immunotherapy with larger doses of allodepleted T-cells after haplo-SCT, enhancing graft versus leukaemia and anti-viral effects."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Selective allodepletion to improve anti-viral and anti-leukaemic responses after haploidentical transplantation"]}]}],"canonical_facts":{"dc:creator":["Samarasinghe, S."],"dc:date":["2009-03"],"dc:date.issued":["2009-03"],"dc:description.abstract":["Immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical SCT, but infection and leukaemic relapse remain problematic. To develop a rational approach to refining allodepletion, we characterized the expression of surface markers and cytokines on proliferating alloreactive T-cells flow cytometrically. CD25 was expressed on 83 % of CFSE-dim alloreactive T-cells, confirming this as an excellent target for allodepletion. 70 % of the alloreactive CD25-ve population expressed CD71, identifying this as a novel marker to target alloreactive T-cells that persist after CD25 depletion. We compared residual alloreactivity to host or 3rd party after CD25 vs combined CD25/71 immunomagnetic depletion in 8 HLA-mismatched donor-recipient pairs. In 1o MLRs, residual responses to host were undetectable after CD25/71 depletion. In 2o MLRs, CD25/71 depletion resulted in significantly lower residual proliferative response to host than CD25 depletion (median 4.8% of the response of unmanipulated PBMC vs 9.9%, p < 0.01). Likewise, the median residual reactivity to host in IFN-γ ELISPOT assays was significantly lower after combined CD25/71 than CD25 allodepletion (14.1 % vs 54.6%, p < 0.05). Third party responses after CD25/71 allodepletion were equivalent to unmanipulated PBMCs in both assays. In pentamer and IFN-γ ELISPOT assays, anti-viral responses to CMV, EBV and adenovirus were preserved after combined CD25/71 allodepletion. Finally, we showed that CD25/71 allodepleted T-cells can be redirected to recognize and secrete IFN-γ and granzyme B in response to CD19 cell lines and primary ALL blasts through lentiviral transfer of a chimeric αCD19ζ TCR. This strategy may facilitate immunotherapy with larger doses of allodepleted T-cells after haplo-SCT, enhancing graft versus leukaemia and anti-viral effects."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://discovery.ucl.ac.uk/id/eprint/15820/1/15820.pdf"],"dc:language":["en","eng"],"dc:publisher.department":["Institute of Child Health"],"dc:publisher.institution":["UCL (University College London)"],"dc:relation.isreferencedby":["https://discovery.ucl.ac.uk/id/eprint/15820/"],"dc:subject":["Molecular Immunology Unit"],"dc:title":["Selective allodepletion to improve anti-viral and anti-leukaemic responses after haploidentical transplantation"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"]},"updated_at":"2026-07-24T05:10:54Z"}