Dual-aptamer-engineered M1 macrophage with enhanced specific targeting and checkpoint blocking for solid-tumor...

Area of Science:

• Biomedical Engineering
• Cancer Therapy
• Immunology

Background:

• Chimeric antigen receptor T (CAR-T) cell therapy shows limited efficacy in solid tumors.
• Genetically engineered macrophages offer therapeutic potential but face challenges like protein expression heterogeneity and toxicity.

Purpose of the Study:

• To develop a simple, non-genetic macrophage engineering strategy for solid tumor treatment.
• To evaluate the efficacy of aptamer-engineered M1 macrophages (ApEn-M1) in targeting and eliminating solid tumors.

Main Methods:

• Utilized glycan metabolic labeling and click chemistry for non-genetic macrophage engineering.
• Developed aptamer-engineered M1 macrophages (ApEn-M1) for enhanced cell-surface targeting.
• Assessed ApEn-M1 efficacy in vitro, in vivo using breast cancer xenograft and metastasis models, and analyzed tumor microenvironment changes.

Main Results:

• ApEn-M1 exhibited enhanced active targeting of tumor cells and significant in vitro/in vivo cytotoxicity.
• Demonstrated superior antitumor efficacy in breast cancer models, including lung metastasis.
• Showed reprogramming of the tumor immune microenvironment, increasing T cell infiltration and activity.
• Confirmed no obvious systemic side effects associated with ApEn-M1 administration.

Conclusions:

• Nongenetic glycan metabolic labeling and click reaction provide an effective strategy for macrophage engineering.
• ApEn-M1 represents a promising cell-based therapy for solid tumors with enhanced targeting and immunomodulatory capabilities.
• This approach expands non-genetic cell engineering strategies for therapeutic applications.