1. Evaluation of Attenuated Tumor Antigens and the Implications for Peptide-Based Cancer Vaccine Development
- Author
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George E. Peoples, Alfred F. Trappey, Guy T. Clifton, Julia M. Greene, D F Hale, Timothy J. Vreeland, Garth S. Herbert, John S. Berry, Doreen O. Jackson, and Mark O. Hardin
- Subjects
chemistry.chemical_classification ,J65 ,medicine.medical_treatment ,E39 ,Peptide ,Stimulation ,Biology ,Folate binding protein ,folate receptor alpha ,03 medical and health sciences ,CTL ,0302 clinical medicine ,Immune system ,Cytokine ,Oncology ,chemistry ,Antigen ,Immunity ,030220 oncology & carcinogenesis ,Immunology ,medicine ,Cancer vaccine ,E39' ,Research Paper ,030215 immunology - 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.
- Published
- 2017
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