Abstract 471: A new synthetic peptide DS-2 enhanced anti-tumor activity by targeting human telomerase reverse transcriptase (hTERT) in prostate cancer cells

Abstract Human telomerase reverse transcriptase (hTERT) is overexpressed in most human cancers. Therefore, hTERT is considered as an important target for cancer therapy. In the present study, we synthetized a new peptide, DS-2, based on the telomerase vaccine GV1001, a 16-mer peptide. The aim of this study is to evaluate the molecular mechanism of DS-2 on the anticancer activity by targeting hTERT in prostate cancer cells. The expression levels of hTERT in prostate cancer patients were measured. We compared the cytotoxic activity of GV1001 and DS-2 against different prostate cancer cell lines. Flow cytometry was used to evaluate the effects of DS-2 on apoptosis. The scratch-wound assay and matrigel invasion assay were performed to determine the metastasis ability of prostate cancer cells. We further measured the telomerase enzyme activity of DS-2 in LNCaP cells. Furthermore, tumor-bearing nude mice were employed to evaluate the anticancer effect of GV1001 and DS-2. The cytotoxicity of human peripheral blood mononuclear cells (PBMC) on prostate cancer cells was determined by lactate-dehydrogenase (LDH)-release assay. The hTERT expression was directly correlated with telomerase activity in LNCaP cells, and DS-2 significantly inhibited telomerase enzyme activity, resulting in reducing LNCaP cells proliferation and metastasis. Furthermore, DS-2 exhibited the most substantial anti-cancer potential against prostate cancer cells compared with different cancer cell lines. In the tumor-bearing nude mice model, DS-2 significantly inhibited the growth of the prostate tumor and downregulated the expression of hTERT and Ki-67 in the tumor tissue as evidenced by western blot and immunohistochemistry analysis, respectively. Furthermore, the potent cytotoxicity was exhibited in LNCaP cells after treated with DS-2-activated PBMC plus IL-2. In addition, DS-2 synergistically enhanced IL-2 production from activated PBMC. These data indicated that the inhibition of hTERT expression by DS-2 suppressed prostate cancer cell growth and induced anti-cancer immunity. Therefore, DS-2 might be used as a novel therapeutic drug for cancer immunotherapy by targeting hTERT in prostate cancer. Citation Format: Jae Hyeon Park, Joo Kyung Shin, Joo Hee Han, Hyung Sik Kim. A new synthetic peptide DS-2 enhanced anti-tumor activity by targeting human telomerase reverse transcriptase (hTERT) in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 471.