Efficient Regeneration of Human Vα24+ Invariant Natural Killer T Cells and Their Anti-Tumor Activity In Vivo

Jul 17, 2016Stem cells (Dayton, Ohio)

Fast Regrowth of a Special Type of Human Immune Cells and Their Ability to Fight Tumors in the Body

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Abstract

Induced pluripotent stem cells derived from human invariant NKT cells can produce interferon-γ and demonstrate enhanced cytotoxicity against tumor cells.

A protocol was established to reprogram human invariant NKT cells into induced pluripotent stem cells.
The derived iPS-Vα24iNKT cells can be re-differentiated into functional iNKT cells.
Upon activation by ligand-pulsed dendritic cells, these iPS-Vα24iNKT cells produce a large amount of interferon-γ.
iPS-Vα24iNKT cells exhibit superior cytotoxic activity against various tumor cell lines compared to parental Vα24iNKT cells.
In tumor-bearing mice, iPS-Vα24iNKT cells show significant anti-tumor activity and can activate autologous NK cells.

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Reprogramming of antigen-specific T lymphocytes into induced pluripotent stem cells (iPSCs) and their subsequent re-differentiation has enabled expansion of functional T lymphocytes in vitro, thus opening up new approaches for immunotherapy of cancer and other diseases. In this study, we have established a robust protocol to reprogram human invariant NKT (Vα24iNKT) cells, which have been shown to act as cellular adjuvants and thus exert anti-tumor activity in mice and humans, and to re-differentiate the iNKT cell-derived iPSCs into functional iNKT cells. These iPSC-derived iNKT cells (iPS-Vα24iNKT cells) can be activated by ligand-pulsed dendritic cells (DCs) and produce a large amount of interferon-γ upon activation, as much as parental Vα24iNKT cells, but exhibit even better cytotoxic activity against various tumor cell lines. The iPS-Vα24iNKT cells possess significant anti-tumor activity in tumor-bearing mice and can activate autologous NK cells upon activation by ligand-pulsed DCs in the NOG mouse model in vivo, further extending their therapeutic potential. This study thus provides a first proof of concept for the clinical application of human iPS-Vα24iNKT cells for cancer immunotherapy. Stem Cells 2016;34:2852-2860. + + + + +

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