Catalysis

Polymerization

Molecular biology

Biology

Peptide

Cancer research

Biochemistry

Melanoma

Stereochemistry

Immunology

Polymer

Combinatorial chemistry

Cancer immunotherapy

Organic chemistry

Immune system

Antigen

In vitro

Enzyme

Internal medicine

Cytotoxic T cell

Antigen presentation

Tripeptide

Medicine

Chemistry

Immunotherapy

Epitope

Cancer

Journal of the American Chemical Society

Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivo study on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.

A Strategy Based on the Enzyme-Catalyzed Polymerization Reaction of Asp-Phe-Tyr Tripeptide for Cancer Immunotherapy