An essential step for
cancer vaccination is to break the immunosuppression and elicit a
tumor-specific immunity. A major hurdle against
cancer therapeutic vaccination is the insufficient immune stimulation of the
cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel
cancer immunostimulant,
trichosanthin (TCS), that is a clinically used
protein drug in China, and developed a well-adaptable
protein-engineering method for making
recombinant protein vaccines by fusion of an antigenic
peptide, TCS, and a
cell-penetrating peptide (
CPP), termed an "all-in-one"
vaccine, for transcutaneous
cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the
vaccines was investigated using the different
tumor models. The
vaccines were prepared via a facile recombinant method. The
vaccines induced the maturation of DCs that subsequently primed CD8+ T cells. The TCS-based immunostimulation was associated with the
STING pathway. The general applicability of this genetic engineering strategy was demonstrated with various
tumor antigens (i.e.,
legumain and TRP2 antigenic
peptides) and
tumor models (i.e., colon
tumor and
melanoma). These findings represent a useful protocol for developing
cancer vaccines at low cost and time-saving, and demonstrates the adjuvant application of TCS-an old drug for a new application.