J Cancer 2017; 8(7):1255-1262. doi:10.7150/jca.16450

Research Paper

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

JS Berry1✉, TJ Vreeland2, DF Hale1, DO Jackson3, AF Trappey3, JM Greene3, MO Hardin4, GS Herbert3, GT Clifton5, GE Peoples6✉

1. Department of Surgery, Division of Colon and Rectal Surgery, Washington University, St. Louis, MO;
2. Department of Surgery, Womack Army Medical Center, Fort Bragg, NC;
3. Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX;
4. Department of Surgery, Madigan Army Medical Center, Fort Lewis, WA;
5. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX;
6. Cancer Vaccine Development Program, San Antonio, TX and Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD.

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Citation:
Berry JS, Vreeland TJ, Hale DF, Jackson DO, Trappey AF, Greene JM, Hardin MO, Herbert GS, Clifton GT, Peoples GE. Evaluation of Attenuated Tumor Antigens and the Implications for Peptide-Based Cancer Vaccine Development. J Cancer 2017; 8(7):1255-1262. doi:10.7150/jca.16450. Available from http://www.jcancer.org/v08p1255.htm

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Abstract

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.

Keywords: Folate binding protein, folate receptor alpha, J65, E39, E39'.