Sustained Release of XXXX From a Modular Peptide-Based Cancer Vaccine Alters Vaccine Microenvironment and Enhances the Antigen-Specific T-Cell Response.

@entity5 @entity62512 @entity137 @entity2841
SUMMARY: The recent identification and molecular characterization of @entity5 antigens provides the opportunity to explore the rational development of peptide-based @entity5 vaccines. However, the response to these vaccines remains variable, and peptide-based @entity5 vaccines may even produce tolerance induction and enhanced @entity5 growth. The authors have developed a unique method for the isolation of a polysaccharide polymer of chemically pure @entity62512 ( @entity62512 ). This highly purified polysaccharide can be formulated into a stable gel matrix (designated F2 gel matrix) with unique properties of a sustained-release delivery system that has previously been shown to be an effective immune adjuvant. F2 gel matrix is capable of providing sustained release of antigenic peptide and cytokine in vitro. The purposes of this study were to characterize the ability of F2 gel matrix to provide sustained local release of cytokines in vivo and to test the hypothesis that such sustained release can enhance the microenvironment for antigen presentation, leading to a more effective antitumor response. Subcutaneous administration of F2 gel/cytokine matrix resulted in sustained release of cytokine at the vaccine site for up to 120 hours. Sustained release of @entity2841 ( @entity2841 ) was associated with an increased inflammatory infiltrate at the vaccine site and enhanced dendritic cell activation. Further, accination with F2 gel/SIINFEKL/ @entity2841 matrix resulted in enhanced antigen-specific immunity. Addition of @entity2841 to the F2 gel matrix resulted in an increase in the percentage of antigen-specific T cells in the draining lymph nodes, enhanced @entity137 , a sustained presence of antigen-specific T cells in the peripheral blood, and protection from E.G7 @entity5 challenge. These results support the potential of an F2 gel matrix modular vaccine delivery system that can provide sustained local release of cytokine in vivo, and confirm the powerful effects of @entity2841 as an immune adjuvant.
