Evaluation of Attenuated Tumor Antigens and the Implications for Peptide-Based Cancer Vaccine Development

INTRODUCTION: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death ( AICD), decreasing efficacy. We engineered variants of an immunogenic peptide ( E39) and tested their ability to induce a robust, sustainable immune response. METHODS: Multiple variants of E39 were created by exchanging 1 or 2 amino acids. We tested the PBMC proliferation, cytokine production and cytolytic activity induced by each variant peptide. RESULTS: Repeated stimulation with E39 likely led to in vitro AICD, while stimulation with E39' led to T-cell proliferation with less evidence of AICD, modest cytokine production and high CTL activity. CONCLUSIONS: E39' appears to be the optimal variant of E39 for inducing effective long-term immunity.