Journal
CELL STEM CELL
Volume 12, Issue 1, Pages 114-126Publisher
CELL PRESS
DOI: 10.1016/j.stem.2012.11.002
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Funding
- Project for Realization of Regenerative Medicine
- Global Center of Excellence program from MEXT of Japan
- Japan Society for the Promotion of Science
- Ministry of Health, Labor, and Welfare of Japan
- Grants-in-Aid for Scientific Research [23592022, 24390257, 23249015, 23591413] Funding Source: KAKEN
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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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