A new tumor vaccine: FAPτ-MT elicits effective antitumor response by targeting indolamine-2,3-dioxygenase in antigen presenting cells

Abstract

Indolamine-2,3-dioxygenase (IDO) is expressed in tumor antigen presenting cells (AP Cs) 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 AP Cs 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 FAP α-positive tumor model, the FAPτ-MT vaccine elicited an antitumor 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 failure 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. © 2011 Landes Bioscience.