A Customizable Antibody Delivery Strategy Using Fc-Affinity Ligands

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Controlled release of therapeutic proteins, particularly antibodies, from hydrogel systems is crucial for effective treatment.
• Harnessing noncovalent interactions offers a versatile platform for affinity-controlled protein delivery.

Purpose of the Study:

• To develop and evaluate a novel strategy for the controlled release of native antibodies from hydrogels using affinity interactions.
• To engineer peptide ligands targeting the Fc region of human IgG1 for immobilization within hydrogels.

Main Methods:

• Engineered two Fc-binding ligands (FcL1 and FcLPEG) with varying affinities (K_D) for the Fc region of human IgG1.
• Immobilized ligands within chemically cross-linked hyaluronan-oxime hydrogels and physically cross-linked hyaluronan-methylcellulose hydrogels.
• Investigated the release kinetics of therapeutic antibodies (bevacizumab, adalimumab) from the hydrogel systems.

Main Results:

• Controlled release of bioactive bevacizumab was achieved using the higher-affinity FcL1 ligand in a hyaluronan-oxime hydrogel.
• The lower-affinity FcLPEG ligand did not facilitate controlled release.
• Tunable release of multiple IgG1 antibodies over a 7-day period was demonstrated in a hyaluronan-methylcellulose hydrogel system.

Conclusions:

• The developed affinity-controlled release strategy is broadly applicable for tuning antibody delivery from hydrogels.
• This approach enables precise control over the release of therapeutic antibodies, enhancing their potential clinical utility.