Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

GM-CSF delivery enhances the antigen specific T-cell response to a novel peptide-based cancer vaccine

CL Nguyen MD, JT Bui BS, M Demcheva PhD, JN Vournakis PhD, DJ Cole MD, A Seth PhD, WE Gillanders MD

Marine Polymer Technologies, Inc, Danvers, MA and Medical University of South Carolina, Charleston, SC,

AIM: We have characterized a peptide-based vaccine delivery system utilizing the unique polymer poly-N-acetyl glucosamine, designated the F2 gel. The F2 gel is capable of providing sustained release of antigenic peptide and cytokine in vivo, establishing a potent microenvironment for antigen presentation. The objective of this work is to define the mechanisms and kinetics of antigen-specific T cell responses to the F2 gel vaccine. METHODS: OT-1 T cells express a transgenic T cell receptor specific for H-2Kb and the SIINFEKL peptide. OT-1 T cells (Ly5.2+) were adoptively transferred into congenic B6.SJL recipients. Recipient mice were rested for 24 hours and then vaccinated. OT-1 T cell proliferation in the draining lymph nodes (DLN) and peripheral blood (PBL) was determined by flow cytometry. OT-1 T cell cytotoxic capacity was determined by 51Cr-release assays. RESULTS: Vaccination with F2 gel/SIINFEKL resulted in the in vivo expansion of OT-1 T cells (5.2% in DLN), and in the development of measurable cytotoxic capacity (25.7% lysis of EL-4/SIINFEKL targets). Addition of GM-CSF to the matrix significantly enhanced this OT-1 T cell response (7.7% in the DLN and 52.2% lysis of EL-4/SIINFEKL target). Survey of PBL following vaccination with F2 gel/SIINFEKL/GM-CSF revealed a similar peak at day 3 (2.31 ± 0.26%) followed by a sustained response which persisted over 7 days. CONCLUSIONS: We have established an innovative model to study the response of antigen-specific T cells to the F2 gel vaccine. Delivery of GM-CSF as a part of this novel vaccine enhances the T cell proliferative response and significantly augments T cell cytotoxicity.

KEY WORDS: cancer vaccine, F2 gel, poly-N-acetyl glucosamine.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.