Background:
T-cells are potentially curative for patients with metastatic cancer, but many patients with cancer have T-cells that are terminally differentiated , a condition associated with treatment failure. We have observed that less differentiated T-cells have a greater capacity to proliferate, persist, and destroy large cancer deposits. Advances in regenerative medicine might allow the generation of rejuvenated T-cells from induced pluripotent stem cells (iPSC).
Objectives:
To reprogram patient specimens into induced pluripotent stem cells (iPSC) and differentiate them into different types of somatic cells with the goal to produce cancer antigen-specific T-cells.
To make stored specimens and/or data available to approved research laboratories and investigators.
Eligibility:
Patients enrolled on the National Cancer Institute Surgery Branch (NCI-SB) Cell Harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).
Patients willing to be consented on this protocol.
Design:
Cells and tissue obtained previously under protocol 03-C-2077.
Reprogramming of cells and tissue into iPSC lines.
Derivation of iPSC lines into T-cells and iPSC progeny capable of supporting T-cell differentiation.
Generation of an iPSC-derived thymic organoid.
Screening of tumor antigen specificity for regenerated T-cells.
In vivo analysis of regenerated T-cells.
