Targeting hypersialylation via lectin-directed protein aggregation therapy (LPAT) for anti-metastasis applications

Area of Science:

• Biotechnology
• Cancer Research
• Glycobiology

Background:

• Metastatic cancer poses a significant therapeutic challenge due to its invasive nature.
• Current lectin-based therapies face limitations such as hemagglutination.
• Targeting specific cell surface glycans offers a potential strategy for selective cancer treatment.

Purpose of the Study:

• To develop a novel lectin-directed protein aggregation therapy (LPAT) for targeting metastatic tumor cells.
• To assess the efficacy and safety of LPAT in preclinical models.
• To overcome limitations of traditional lectin-based targeting systems.

Main Methods:

• LPAT agents were engineered by combining multivalent lectins with bacterial microcompartment proteins.
• LPAT agents were screened against breast cancer cell lines for anti-adhesive and anti-invasive activity.
• Efficacy was evaluated in a metastatic mouse model to assess the prevention of lung metastases.

Main Results:

• The most potent LPAT agent demonstrated preferential anti-adhesive and anti-invasive activity against hypersialylated/MMP9 overexpressing MDA-MB-231 cells.
• LPAT agents showed no hemagglutination activity, indicating improved safety.
• LPAT treatment significantly prevented the formation of experimental lung metastases in a mouse model.

Conclusions:

• LPAT represents a promising new strategy for glycan-targeting therapy against metastatic tumors.
• The developed LPAT system is selective for cancer cells and exhibits a favorable safety profile.
• This approach offers a foundation for developing safe and effective treatments to prevent cancer metastasis.