科研之友
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摘要
Indolamine-2,3-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 antitumor 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, FAP tau-MT, which was produced by conjugating 1-MT to a tumor-associated antigen, fibroblast activation protein alpha (FAP alpha). The results in vitro confirmed that 1-MT could be dissociated from the FAP tau-MT vaccine and inhibit intracellular IDO activity. In an FAP alpha-positive tumor model, the FAP tau-MT vaccine elicited an antitumor response which was similar to systemic treatment with the FAP tau vaccine plus 1-MT. Most importantly, administration of the FAP tau-MT vaccine did not lead to pregnancy failure in mice carrying allogeneic fetuses. These findings that FAP tau-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.
