Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix

• Published in: Clinical cancer research 1997-06, Vol.3 (6), p.867-873
• Main Authors: D J Cole, S Gattoni-Celli, E F McClay, J S Metcalf, J M Brown, N Nabavi, D A Newton, 3rd, C B Woolhiser, M C Wilson, J N Vournakis
• Format: Article
• Language: English
• Subjects: Acetylglucosamine; Animals; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - metabolism; Antineoplastic agents; Biocompatible Materials; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cytokines - administration & dosage; Cytokines - pharmacokinetics; Delayed-Action Preparations; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacokinetics; Humans; Immunotherapy; Jurkat Cells; MART-1 Antigen; Medical sciences; Mice; Mice, Inbred C57BL; Neoplasm Proteins - administration & dosage; Neoplasm Proteins - pharmacokinetics; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacokinetics; Pharmacology. Drug treatments; Polysaccharides; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacokinetics
• ISSN: 1078-0432; 1557-3265

Identification of tumor-associated antigens (TAAs) and their class I MHC-restricted epitopes now allows for the rational design of peptide-based cancer vaccines. A biocompatible system capable of sustained release of biologically relevant levels of cytokine and TAA peptide could provide a more effective microenvironment for antigen presentation. Our goal was to test a sustained-release cytokine/TAA peptide-based formulation using a highly purified polysaccharide [poly-N-acetyl glucosamine (p-GlcNAc)] polymer. Granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microgram) and MART-1(27-35) peptide (128 microgram in DMSO) were formulated into p-GlcNAc. Peptide release was assayed in vitro using interleukin 2 production from previously characterized MART-1(27-35)-specific Jurkat T cells (JRT22). GM-CSF release was assayed via ELISA and proliferation of M-07e (GM-CSF-dependent) cells. Local bioavailability of MART-1(27-35) peptide for uptake and presentation by antigen-presenting cells was demonstrated for up to 6 days (>0.5 microgram/ml). More than 1.0 microgram/ml GM-CSF was concomitantly released over the same period. Biocompatibility and local tissue response to p-GlcNAc releasing murine GM-CSF was determined in C57BL/6 mice via s.c. injection using murine GM-CSF (0. 2 microgram/ml) in 200 microliter of a 2.5% polymer gel. Significant lymphocytic and eosinophilic infiltration was observed 2-7 days after injection with polymer containing murine GM-CSF. The results of our studies show that this biocompatible system is capable of a sustained concomitant release of biologically active peptide and cytokine into the local microenvironment. These findings support further studies to validate a p-GlcNAc delivery system vehicle for a cytokine/TAA peptide-based cancer vaccine.