Abstract LB-173: Epitope mapping of mTERT for vaccine development

Abstract

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 (mTERT) with high immunogenicity via epitope mapping using two approaches. The first one consists in washing off the MHC I-bound mTERT peptides (Mild Acid Elution; MAE) from the cell surface of mTERT-overexpressing cells (SPON-10-mTERT cells generated from spontaneous lung tumors developed in an A/J mouse), followed by mass spectrometry analysis. The initial mass spec analysis showed one 14-mer peptide from MAE with 22 PSMs, with a good XCorr score compared to peptide from PBS elution control with only 1 PSMs, with lower XCorr score. The second approach is to inject overlapping mTERT peptides covering the whole protein sequence in mice, and then splenocytes from these mice will be stimulated in vitro using mTERT peptide library to determine immunogenic peptides. Both approaches are in progress to identify potential mTERT epitopes. Funded by NCI Contract No. HHSN261200800001E Citation Format: Yurong Song, Jason Marshall, Sudipto Das, Thorkell Andresson, Amanda Corbel, Shizuko Sei, Robert H. Shoemaker, Ligia Pinto. Epitope mapping of mTERT for vaccine development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-173.