Acid-Degradable Particles for Protein-Based Vaccines:  Enhanced Survival Rate for Tumor-Challenged Mice Using Ovalbumin Model

• Published in: Bioconjugate chemistry 2004-11, Vol.15 (6), p.1281-1288
• Main Authors: Standley, Stephany M, Kwon, Young Jik, Murthy, Niren, Kunisawa, Jun, Shastri, Nilabh, Guillaudeu, Steven J, Lau, Lana, Fréchet, Jean M. J
• Format: Article
• Language: English
• Subjects: Animals; Cancer Vaccines - administration & dosage; Cancer Vaccines - chemistry; Cancer Vaccines - metabolism; Cellular biology; Cross-Linking Reagents - administration & dosage; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - metabolism; Drug Delivery Systems - methods; Female; Hydrogen-Ion Concentration; Mice; Mice, Inbred C57BL; Ovalbumin - administration & dosage; Ovalbumin - metabolism; Polymers; Proteins; Survival Rate; Tumors; Vaccines
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc049956f

Acid-degradable protein-loaded polymer particles show promise for antigen-based vaccines due to their ability to activate cytotoxic T lymphocytes (CTLs) in vitro. Protein loadings and cytotoxic T lymphocyte activation efficiencies have now been enhanced through novel delivery vehicle designs. In particular, the use of a more hydrophilic acid-degradable cross-linker leads to increased water dispersibility and increased protein loading efficiency for the particles. A 2.5-fold increase in protein encapsulation allows the delivery of more protein antigen to antigen presenting cells (APCs) leading to a 20-fold rise in antigen presentation levels. The mechanism by which APCs internalize these particles was explored using the phagocytosis inhibitor, cytochalasin B. In addition, preliminary in vivo experiments were conducted to investigate the ability of the protein-loaded particles to provide immunity against tumors in mice, and an enhanced survival rate over the use of protein alone was observed, indicating that this vaccine delivery strategy has great practical potential.