A Shear-Thinning Biomaterial-Mediated Immune Checkpoint Blockade

Area of Science:

• Biomaterials Science
• Immunology
• Oncology

Background:

• Systemic immune checkpoint blockade (ICB) shows variable efficacy and toxicity.
• Local ICB delivery offers potential for enhanced therapeutic effects and reduced side effects.
• Targeting programmed cell death protein 1 (PD-1) is a key strategy in cancer immunotherapy.

Purpose of the Study:

• To develop a minimally invasive strategy for local delivery of anti-PD-1 using shear-thinning biomaterials (STBs).
• To investigate the controlled release of anti-PD-1 from STBs.
• To evaluate the efficacy of locally delivered anti-PD-1 in a preclinical cancer model.

Main Methods:

• Formulation of STBs with gelatin and Laponite silicate nanoplatelets.
• Loading of anti-PD-1 into STBs (STB-ICI).
• Assessment of ICI release kinetics influenced by Laponite content and pH.
• Evaluation of STB-ICI efficacy in a murine melanoma model, analyzing tumor growth and immune cell infiltration.

Main Results:

• STB-ICI demonstrated controlled release of anti-PD-1, modulated by Laponite concentration and local pH.
• Local injection of STB-ICI significantly inhibited tumor growth in the murine melanoma model.
• STB-ICI treatment led to increased CD8+ T cell levels in peripheral blood and enhanced infiltration of CD4+ helper T cells and CD8+ cytotoxic T cells within tumors.
• Increased tumor cell death was observed following STB-ICI administration.

Conclusions:

• STB-based local delivery of anti-PD-1 is a simple and effective strategy for cancer immunotherapy.
• This approach enhances anti-tumor immune responses and reduces tumor progression.
• Minimally invasive local delivery of ICIs holds promise for improved cancer treatment outcomes.