2012
DOI: 10.1182/blood-2011-07-366419
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Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells

Abstract: The adoptive transfer of donor T cells that have been genetically modified to recognize leukemia could prevent or treat leukemia relapse after allogeneic HSCT (allo-HSCT). However, adoptive therapy after allo-HSCT should be performed with T cells that have a defined endogenous TCR specificity to avoid GVHD. Ideally, T cells selected for genetic modification would also have the capacity to persist in vivo to ensure leukemia eradication. Here, we provide a strategy for deriving virus-specific T cells from CD45RA… Show more

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Cited by 177 publications
(153 citation statements)
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“…Persistent memory phenotypes have been correlated with complete remissions in CAR-T-cell therapy clinical trials for leukemia (38). To understand whether the switch dose can influence IgG4m sCAR-T-cell populations, we dosed NSG mice bearing the Nalm-6 tumor xenograft with 0.05-, 0.5-, or 2.5-mg/kg LCNT switch and analyzed the expression of CD45RA and CD62-L on CD4 + and CD8 + T cells in peripheral blood after 21 d (5 d after the final dose).…”
Section: Site and Valency Of Pne Engraftment Affects Scar-t-cell Potementioning
confidence: 99%
“…Persistent memory phenotypes have been correlated with complete remissions in CAR-T-cell therapy clinical trials for leukemia (38). To understand whether the switch dose can influence IgG4m sCAR-T-cell populations, we dosed NSG mice bearing the Nalm-6 tumor xenograft with 0.05-, 0.5-, or 2.5-mg/kg LCNT switch and analyzed the expression of CD45RA and CD62-L on CD4 + and CD8 + T cells in peripheral blood after 21 d (5 d after the final dose).…”
Section: Site and Valency Of Pne Engraftment Affects Scar-t-cell Potementioning
confidence: 99%
“…While T cells modified to express a CAR respond to ligation of either the CAR or their naïve TCR, the impact of signaling through a CAR instead of a TCR has not been completely characterized [13]. The greater affinity of a scFv for target antigen compared with the affinity of a native TCR for its cognate peptide-MHC complex may be advantageous in promoting high-avidity interaction between the modified T cell and tumor, as supported by the finding that targeting of ROR1 ?…”
Section: Design Of Chimeric Antigen Receptorsmentioning
confidence: 90%
“…Two recent reports have suggested that CD19-specific CAR-modified T cell therapy may have anti-tumor activity in allogeneic hematopoietic stem cell transplant (HCT) recipients [54,60]. The concern that administration of allogeneic CAR-modified T cells that express endogenous potentially alloreactive TCRs could exacerbate graft versus host disease (GVHD) stimulated development of strategies to CAR-modify virus-specific T cells, which have been shown to have a lower risk of causing GVHD after adoptive transfer [13,54,61]. However, in the limited number of patients treated to date, therapy with allogeneic CARmodified unselected T cells was not associated with severe GVHD [54,60].…”
Section: Clinical Trialsmentioning
confidence: 99%
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