Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy
Immune Network
; : 134-139, 2016.
Article
Dans En
| WPRIM
| ID: wpr-168214
Responsable en Bibliothèque :
WPRO
ABSTRACT
Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Lymphocytes
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Lymphocytes T
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Lymphocytes T cytotoxiques
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Zidovudine
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Auto-immunité
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Anticorps bloquants
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Transfert adoptif
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Thérapie cellulaire et tissulaire
Limites du sujet:
Animals
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Humans
langue:
En
Texte intégral:
Immune Network
Année:
2016
Type:
Article