[PDF][PDF] Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation

T Nishimura, S Kaneko, A Kawana-Tachikawa… - Cell stem cell, 2013 - cell.com
T Nishimura, S Kaneko, A Kawana-Tachikawa, Y Tajima, H Goto, D Zhu…
Cell stem cell, 2013cell.com
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 high proliferative capacity and …
Summary
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 high proliferative capacity and elongated telomeres. These "rejuvenated" cells possessed antigen-specific killing activity and exhibited T cell receptor gene-rearrangement patterns identical to those of the original T cell clone from the patient. We also found that this method can be effective for generating specific T cells for other pathology-associated antigens. Thus, this type of approach may have broad applications in the field of adoptive immunotherapy.
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