About the Cover: The image is a visual allegory of the generation of iTEs (in red). It was designed and illustrated by Michael J. Kruhlak, Ph.D., from the Experimental Immunology Branch, CCR, NCI.
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs). iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies.
Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System. Vizcardo R, Klemen ND, Islam SMR, Gurusamy D, Tamaoki N, Yamada D, Koseki H, Kidder BL, Yu Z, Jia L, Henning AN, Good ML, Bosch-Marce M, Maeda T, Liu C, Abdullaev Z, Pack S, Palmer DC, Stroncek DF, Ito F, Flomerfelt FA, Kruhlak MJ, Restifo NP. Cell Rep. 2018 Mar 20;22(12):3175-3190.