{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou X"],"funding":["NHLBI NIH HHS","NCI NIH HHS"],"pagination":["3895-905"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4064331"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["123(25)"],"pubmed_abstract":["Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892."],"journal":["Blood"],"pubmed_title":["Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene."],"pmcid":["PMC4064331"],"funding_grant_id":["P30CA125123","P01 CA094237","P01CA094237","P50CA126752","P50 CA126752","U54HL08100","P30 CA125123"],"pubmed_authors":["Leung KS","Liu H","Di Stasi A","Wu MF","Rooney CM","Spencer DM","Durett AG","Zhou X","Tey SK","Gee AP","Dotti G","Grilley BJ","Lin YF","Brenner MK","Martinez C","Heslop HE","Krance RA","Leen AM","Savoldo B"],"additional_accession":[]},"is_claimable":false,"name":"Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.","description":"Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jun","modification":"2020-11-19T11:56:30Z","creation":"2019-03-27T01:30:31Z"},"accession":"S-EPMC4064331","cross_references":{"pubmed":["24753538"],"doi":["10.1182/blood-2014-01-551671"]}}