Abstract 5090: Epitope mapping of mouse TERT for vaccine development

Abstract

Telomerase reverse transcriptase (TERT) is one of two essential components of telomerase, an enzyme complex that generates and maintains telomeres. Telomerase is expressed mainly in embryonic and adult stem cells. Telomere biology has recently been implicated in the pathogenesis of a variety of diseases, and mutations in telomerase components result in a predisposition to solid malignancies. More recent findings show that TERT is not only expressed in late stage primary tumor cells and metastatic cells, but also expressed in incipient cancer stem cells and/or tumor-initiating cells, indicating that TERT has essential roles at every stage of tumorigenesis. However, the clinical benefit of a TERT (hTERT)-targeting vaccine, given as a single agent or in combination with chemotherapeutic agents, has been limited in patients with advanced cancer, possibly due to insufficient epitope coverage as well as tumor-induced immune suppression. Thus, targeting TERT in tumor-initiating cells in early stage lesions may be more effective in preventing cancer development and progression. To develop cancer preventive TERT vaccines, novel immunogenic epitopes must be first identified and evaluated in a relevant preclinical model of tumorigenesis. The goal of this project is to identify the epitopes of mouse TERT with high immunogenicity using MHC I-peptide binding assay by flow cytometry analysis. The in vitro peptide-induced MHC Class I stabilization assay was carried out using RMA/S cell line, which was derived from a Rauscher leukemia virus-induced C57BL/6 T cell lymphoma and is deficient in transporter associated with antigen processing (TAP). Results of screening the overlapping peptide library will be presented. Funded by NCI Contract No. HHSN261200800001E Citation Format: Yurong Song, Jason Marshall, Travis Kerr, Ligia Pinto, Shizuko Sei, Robert Shoemaker. Epitope mapping of mouse TERT for vaccine development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5090.