A new tumor vaccine: FAPtau-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells.

摘要

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