Vol.:(0123456789) 1 3 International Journal of Peptide Research and Therapeutics https://doi.org/10.1007/s10989-018-9683-z Efects of Infuenza Derived Peptide on CD8 T Cell Responses to MHC Class I-Restricted Human Telomerase Reverse Transcriptase (hTERT)- Derived Peptide Jamshid Gholizadeh Navashenaq 1,2  · Arezoo Gowhari Shabgah 1,2  · Esmat Alsadat Hashemi 3  · Mir Hadi Seyedzadeh 1,2  · Fazel Shokri 1  · Seyed Alireza Razavi 1  · Gholam Ali Kardar 2 Accepted: 6 February 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human telomerase reverse transcriptase (hTERT). The main aim of this study was to use an epitope from hTERT accom- panied by an epitope derived from infuenza virus restricted to HLA-A2, a common Class I HLA in Iran, to induce T cells against tumoral cells. The epitopes were analyzed in IEDB and EpiMHC databases for the strength of binding to HLA-A2 and immunogenicity, respectively. Peripheral blood mononuclear cells (PBMCs) from 11 HLA-A2-positive breast cancer patients were isolated and then were harvested and co-cultured with MCF-7 cells that were previously trans-loaded with synthesized peptides. PBMC proliferation, interferon-γ (IFN-γ) secretion, and activated T cell cytotoxicity were analyzed by MTT, ELISA, and LDH cytotoxicity assays, respectively. Proliferation of PBMCs incubated with the tumoral peptide was signifcantly greater than that of controls (P < 0.001). In addition, the proliferation of PBMCs incubated with tumoral and viral peptides was greater than that of PBMCs incubated with tumoral peptide alone. The same was true of IFN-γ secretion and LDH release (P < 0.001 and P < 0.05 respectively). Tumoral peptide can induce PBMCs through a class I MHC pathway and this induction is intensifed with viral peptides. Keywords Cancer · Bioinformatics · hTERT · Peptide-based vaccine · Viral peptide Introduction Breast tumor is a situation in which malignant cells devi- ate from the breast tissues. Cancerous cells can invade surrounding tissues; however, with early diagnosis and treatment, most patients have normal or near-normal lives (Al-Hajj et al. 2003; Zhou and Zhong 2004). According to the World Health Organization declaration, breast cancer is a leading cause of death among women worldwide, and afects the lives of thousands of women each year (Lacey Jr et al. 2009). Although surgery, chemotherapy, radiother- apy, and hormone therapy have been used for the treatment, approaches for patients with metastatic and invasive breast cancer are not sufcient (Andersen et al. 2008; Emens 2010; Zhou and Zhong 2004). One promising strategy is active specifc immunotherapy, by which established tumors are destroyed through the stimulation of immune responses against tumoral antigens (Bergman 2009; Bertolaccini and Olivero 2001; Finn 2008; Kirkwood et al. 2012; Schultze et al. 2008). The T cell-based immunotherapy uses the anti- tumor cytotoxic T lymphocytes (CTLs) as a weapon to kill tumor cells, and tumor-associated antigens (TAAs) are the targets (June 2007). To date, breast tumor antigens such as Her2/neu, CA 15-3, CA 27.29, and CEA have been identi- fed. However, most TAAs are not expressed by all tumors (Neller et al. 2008; Yi et al. 2009). In addition, the appear- ance of antigen loss mutations in the presence of immune * Seyed Alireza Razavi razavial@tums.ac.ir * Gholam Ali Kardar gakardar@tums.ac.ir 1 Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2 Immunology Asthma & Allergy Research Institute, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran 3 Breast Cancer Research Group, Breast Cancer Research Center (BCRC-ACECR), Tehran, Iran