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Citation
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HERO ID
1103191
Reference Type
Journal Article
Title
A new tumor vaccine: FAPτ-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells
Author(s)
Yi, YM; Zhang, G; Zeng, J; Huang, SC; Li, LL; Fang, R; Jiang, GM; Bu, XZ; Cai, SH; Du, J
Year
2011
Volume
11
Issue
10
Page Numbers
866-873
Language
English
PMID
21372637
Abstract
Indolamine2, 3-dioxygenase (IDO) is expressed in tumor antigen presenting cells (APCs) and plays an important role in tumor immune tolerance. Inhibiting its activity may break tumor immune tolerance and thus promote therapeutic effects. Thus, a specific inhibitor of IDO, 1-methyl-tryptophan (1-MT), is being used more and more frequently in anti-tumor studies. However, IDO also maintains systemic immune balance by suppressing abnormal immune responses. Therefore, targeting IDO in tumor-associated APCs in a way that does not disrupt immune balance warrants further investigation. In this study, we developed a new tumor vaccine, FAPτ-MT, which was produced by conjugating 1-MT to a tumor associated antigen, fibroblast activation protein α (FAPα). The results in vitro confirmed that 1-MT could be dissociated from the FAPτ-MT vaccine and inhibit intracellular IDO activity. In an FAPα-positive tumor model, the FAPτ-MT vaccine elicited an anti-tumor response which was similar to systemic treatment with the FAPτ vaccine plus 1-MT. Most importantly, administration of the FAPτ-MT vaccine did not lead to pregnancy failiure in mice carrying allogeneic fetuses. These findings that FAPτ-MT breaks tumor immune tolerance as a local IDO inhibitor, suggest that conjugation of 1-MT to a tumor antigen peptide is a potentially effective clinical cancer immunotherapy.
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