Selective ablation of tumor-associated macrophages suppresses metastasis and angiogenesis

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Tumor-associated macrophages (TAM) are crucial for tumor progression and metastasis.
• Legumain, an asparaginyl endopeptidase, is highly expressed on the surface of TAM.

Purpose of the Study:

• To investigate the potential of targeting legumain on TAM for cancer therapy.
• To evaluate a novel doxorubicin-based prodrug activated by legumain for selective TAM ablation.

Main Methods:

• Development of a doxorubicin prodrug activated specifically by legumain.
• Administration of the prodrug to murine tumor models.
• Assessment of TAM ablation, angiogenic factors, tumor vessel growth, circulating tumor cells, and tumor growth/metastasis.

Main Results:

• The legumain-activated prodrug selectively ablated TAM.
• Treatment significantly reduced angiogenic factors and tumor vessel growth.
• Circulating tumor cells and myeloid-derived suppressor cells were suppressed.
• Tumor growth and metastasis were greatly inhibited in treated animals.

Conclusions:

• Legumain-activated prodrugs targeting TAM represent a promising novel anticancer strategy.
• Selective TAM ablation can effectively inhibit tumor development and metastasis.