TY - JOUR
T1 - Development and characterization of naive single-type tumor antigen-specific CD8+ T lymphocytes from murine pluripotent stem cells
AU - Lei, Fengyang
AU - Haque, Mohammad
AU - Sandhu, Praneet
AU - Ravi, Swetha
AU - Song, Jianyong
AU - Ni, Bing
AU - Zheng, Songguo
AU - Fang, Deyu
AU - Jia, Hongyan
AU - Yang, Jin Ming
AU - Song, Jianxun
N1 - Publisher Copyright:
© 2017 Taylor & Francis Group, LLC.
PY - 2017/7/3
Y1 - 2017/7/3
N2 - Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice. Three weeks later, B16 melanoma cells were inoculated subcutaneously, and the antitumor activity of the iPSC-derived T cells was assessed. We observed the development of the TRP2-specific iPSC-CD8+ T cells that responded to Ag stimulation and infiltrated into melanoma tissues, significantly inhibited the tumor growth, and improved the survival of the tumor-bearing mice. Thus, this approach may provide a novel effective strategy to treatment of malignant tumors.
AB - Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice. Three weeks later, B16 melanoma cells were inoculated subcutaneously, and the antitumor activity of the iPSC-derived T cells was assessed. We observed the development of the TRP2-specific iPSC-CD8+ T cells that responded to Ag stimulation and infiltrated into melanoma tissues, significantly inhibited the tumor growth, and improved the survival of the tumor-bearing mice. Thus, this approach may provide a novel effective strategy to treatment of malignant tumors.
KW - Cytotoxic T lymphocytes
KW - Pluripotent stem cells
KW - immunotherapy
KW - melanoma, mouse
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U2 - 10.1080/2162402X.2017.1334027
DO - 10.1080/2162402X.2017.1334027
M3 - Article
C2 - 28811978
AN - SCOPUS:85021434247
SN - 2162-4011
VL - 6
JO - OncoImmunology
JF - OncoImmunology
IS - 7
M1 - e1334027
ER -