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.