Antibody-lectin chimeras for glyco-immune checkpoint blockade

Area of Science:

• Immunology
• Glycobiology
• Cancer Biology

Background:

• Checkpoint blockade immunotherapy shows curative potential but faces resistance in many patients.
• Glyco-immune checkpoints, involving cell-surface glycans and lectin receptors, are key mechanisms for cancer immune evasion and therapeutic resistance.

Purpose of the Study:

• To develop a novel modular system, antibody-lectin chimeras (AbLecs), for effective glyco-immune checkpoint blockade in cancer immunotherapy.

Main Methods:

• AbLecs were engineered as bispecific molecules combining a cell-targeting antibody domain with a lectin decoy receptor domain.
• The system was evaluated for its ability to block glycan-lectin interactions and potentiate anti-tumor immune responses in vitro and in vivo.

Main Results:

• AbLecs demonstrated potentiation of cancer cell destruction by human immune cells in vitro.
• In a humanized mouse model, AbLecs significantly reduced tumor burden, outperforming existing therapies.
• AbLecs synergized with established immune checkpoint blockade, indicating a distinct therapeutic axis.

Conclusions:

• AbLecs represent a promising new modality for cancer immunotherapy by targeting glyco-immune checkpoints.
• The modular design allows for broad applicability against various tumors and immune cell subsets.
• AbLecs offer a potential strategy to overcome therapeutic resistance in cancer treatment.