Taken together, these maneuvers significantly improve the biophysicochemical properties and greatly endow Epacasome with the ability to synergise anti-PD-1 therapy for further enhanced tumour reduction, prolonged mouse survival, as well as increased IDO1 suppression and antitumour CTLs responses in a B16–F10 melanoma model without overt systemic toxicities. Here, IDO1 is linked to melanoma.