Retaining antibodies in tumors with a self-assembling injectable system

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Immunology

Background:

• Therapeutic antibodies, such as IgG, often exhibit short in vivo half-lives, limiting their efficacy.
• Localizing antibodies within target tissues, like tumors, is crucial for enhancing therapeutic outcomes.
• Existing delivery methods struggle with sustained and targeted antibody retention.

Purpose of the Study:

• To evaluate an in situ-forming injectable membrane system for retaining and orienting therapeutic IgG molecules in vivo.
• To assess the biological activity and localization of antibodies within the peptide amphiphile membrane.
• To determine the efficacy of the system in prolonging antibody retention within tumor microenvironments.

Main Methods:

• Development of an injectable aqueous mixture of peptide amphiphiles (EAK16-II, EAKH6) and intermediate proteins (anti-H6 antibody, protein A/G).
• Characterization of the membrane structure using scanning electron microscopy.
• In vitro assessment of IgG capture and biological activity.
• In vivo studies in mice with epithelial tumor lines (4T1) and melanoma (B16) to evaluate IgG retention.

Main Results:

• Scanning electron microscopy confirmed IgG molecule localization on the EAK16-II/EAKH6 membrane.
• Captured IgG retained biological activity in vitro.
• The injectable system successfully coassembled into His-tag displaying materials in vivo.
• Fluorescently labeled IgG was retained in 4T1 mouse mammary tumors for up to 120 hours, compared to 24 hours for free IgG.
• Reduced antibody clearance was observed in B16 melanoma models.

Conclusions:

• The injectable peptide amphiphile membrane system effectively immobilizes and retains therapeutic IgG molecules locally in vivo.
• This approach significantly enhances the in vivo retention time of antibodies within tumor tissues.
• The system holds promise for improving the delivery and efficacy of immune modulatory antibodies in cancer therapy.