2013
DOI: 10.1016/j.stem.2012.11.002
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Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation

Abstract: Adoptive immunotherapy with functional T cells is potentially an effective therapeutic strategy for combating many types of cancer and viral infection. However, exhaustion of antigen-specific T cells represents a major challenge to this type of approach. In an effort to overcome this problem, we reprogrammed clonally expanded antigen-specific CD8(+) T cells from an HIV-1-infected patient to pluripotency. The T cell-derived induced pluripotent stem cells were then redifferentiated into CD8(+) T cells that had a… Show more

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Cited by 341 publications
(421 citation statements)
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References 71 publications
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“…To differentiate hES/hiPSCs into hematopoietic cells, we used our previously established protocol [21][22][23]. After pretreating mouse mesenchymal feeder C3H10T1/2 cells with mitomycin C, small clumps (approximately 100 cells) of hES/iPSCs (suspended in phosphate-buffered saline [PBS] containing 0.25% trypsin, 1 mM CaCl 2 , and 20% knockout serum replacement) were transferred onto the C3H10T1/2 cells (8.0 3 10 5 cells per a 100-mm dish) and cultured in differentiation medium supplemented with 20 ng/ml vascular endothelial growth factor for 14 days (day 214 to day 0).…”
Section: Erythroid Differentiation Via Sac Formation From Hes/ipscsmentioning
confidence: 99%
See 1 more Smart Citation
“…To differentiate hES/hiPSCs into hematopoietic cells, we used our previously established protocol [21][22][23]. After pretreating mouse mesenchymal feeder C3H10T1/2 cells with mitomycin C, small clumps (approximately 100 cells) of hES/iPSCs (suspended in phosphate-buffered saline [PBS] containing 0.25% trypsin, 1 mM CaCl 2 , and 20% knockout serum replacement) were transferred onto the C3H10T1/2 cells (8.0 3 10 5 cells per a 100-mm dish) and cultured in differentiation medium supplemented with 20 ng/ml vascular endothelial growth factor for 14 days (day 214 to day 0).…”
Section: Erythroid Differentiation Via Sac Formation From Hes/ipscsmentioning
confidence: 99%
“…We have developed a coculture system with which human ESCs or iPSCs can be differentiated into multipotent hematopoietic progenitors capable of yielding megakaryocytes, erythroblasts, or lymphocytes [21][22][23]27]. Using this culture system, we first sought to generate erythroblasts from the H1 and KhES-3 hESC lines using the protocol diagrammed in Figure 1A and from human CB-CD34 + cells using the protocol diagrammed in Figure 1B.…”
Section: Optimization Of Cell Fixation For Tracing Expression Of Indimentioning
confidence: 99%
“…T cells. There was also evidence that such ''rejuvenated'' cells possessed antigen-specific killing activity and exhibited TCR gene rearrangement patterns identical to those of the original T cell clone from the patient (Nishimura et al 2013). Furthermore, they showed that re-differentiation of these cells produced CD8…”
Section: Transfer Of Exogenous T Cell Receptormentioning
confidence: 95%
“…Similar to ESCs, iPSCs have the capacity for self-renewal and could potentially derive unlimited induction of antigen-specific juvenile T cells. Two stem cell groups have explored this novel approach to reprogram an exhausted immune system as treatment of cancer and chronic infection (Nishimura et al 2013;Vizcardo et al 2013). Both groups successfully established protocols to reprogram human antigen-specific CD8 ?…”
Section: Transfer Of Exogenous T Cell Receptormentioning
confidence: 99%
“…5 In that context, we established an in vitro iPS-Sac culture system for differentiation into megakaryocytes (MKs, platelet precursors), 5,6 which also yields T lymphocytes. 7 Unfortunately, the efficiency of the MK production is extremely low. 5 We therefore established self-renewing immortalized MK progenitor cell lines (imMKCLs) from hiPSCs as a starting material of platelet supply, because they exhibit a capacity for the long-term expansion of MKs that produce a substantial yield of platelets.…”
Section: Introductionmentioning
confidence: 99%