In situ self-assembled glycopeptide regulates tumor microenvironment for tumor immunotherapy

Area of Science:

• Biomedical Engineering
• Immunology
• Nanomedicine

Background:

• Reprogramming tumor-associated macrophages (TAMs) to an antitumor phenotype is a key strategy in tumor immunotherapy.
• Current drugs face challenges in simultaneously repolarizing and activating TAMs for enhanced therapeutic effects.

Purpose of the Study:

• To develop an in situ self-assembled glycopeptide for regulating the tumor microenvironment and enhancing tumor immunotherapy.
• To achieve simultaneous repolarization and activation of TAMs using a novel nanomedicine approach.

Main Methods:

• Development of an in situ self-assembling glycopeptide that targets CD206 and CD47 on TAMs.
• In vitro and in vivo studies to evaluate the glycopeptide's ability to repolarize M2-like TAMs to M1-like and activate M1-like TAMs.
• Assessment of the glycopeptide's tumor retention, blood clearance, and systemic toxicity.

Main Results:

• The glycopeptide selectively targets CD206/CD47 and self-assembles into nanoclusters in situ.
• Repolarization of protumoral M2-like TAMs to antitumoral M1-like TAMs via CD206 blockage and enhanced M1-like TAM activation via CD47 occupancy.
• Significant inhibition of tumor growth in various models due to induced antigen presentation and T cell-mediated adaptive immune responses.

Conclusions:

• The developed glycopeptide effectively reprograms TAMs, offering a promising strategy for tumor immunotherapy.
• The in situ transformation into nanoclusters provides superior tumor retention and reduced systemic toxicity.
• This glycopeptide's multitargeted regulation and in situ transformation properties inspire the design of advanced nanomedicines for cancer treatment.