Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic options and poor prognosis. Conventional treatments such as chemotherapy and radiation yield minimal survival benefits, while surgical resection is feasible only in a small subset of patients due to high recurrence rates and advanced disease presentation. The urgent need for effective therapies has driven interest in gene and immunotherapy approaches targeting tumor-specific antigens. Human telomerase reverse transcriptase (hTERT), a key component of telomerase activity, is overexpressed in approximately 80–90% of HCC cases but largely absent in normal somatic tissues, making it an ideal target for selective cancer therapy.
This study investigated the antitumor effects of a recombinant adenovirus carrying the C-terminal 27-kDa fragment of hTERT (rAdv-hTERTC27) in both in vitro and in vivo models of murine hepatocellular carcinoma. The Hepa 1-6 cell line was used to assess the direct impact of hTERTC27 on tumor cell viability and apoptosis. Treatment with rAdv-hTERTC27 significantly inhibited cell proliferation and induced apoptosis, as confirmed by CCK-8 assays, propidium iodide/Hoechst staining, and cell death ELISA. These findings indicate that hTERTC27 exerts potent cytotoxic effects on HCC cells independent of endogenous telomerase inhibition, thereby minimizing potential harm to healthy proliferative tissues.
Further analysis revealed that dendritic cells transduced with rAdv-hTERTC27 effectively stimulated antigen-specific T-cell responses.Fmoc-PNA-A(Bhoc)-OH Biochemical Assay Reagents Co-culture experiments demonstrated enhanced T-cell proliferation and increased cytotoxicity against Hepa 1-6 targets, particularly at effector-to-target ratios of 20:1 and 40:1.Cyclopentane-1,3-dicarboxylic acid In Vivo This suggests that rAdv-hTERTC27 not only directly kills tumor cells but also activates adaptive immunity through dendritic cell-mediated priming of cytotoxic T lymphocytes.PMID:34410317
In vivo evaluation utilized a syngeneic HCC model in C57BL/6 mice, where Hepa 1-6 cells were implanted under the hepatic capsule. A single intravenous injection of 5×10⁷ pfu rAdv-hTERTC27 resulted in significant tumor growth suppression compared to control groups receiving rAdv-EGFP, PBS, or free hTERTC27 polypeptide. Mean tumor volumes were markedly reduced (1,012±51.63 mm³ vs. 2,567±32.21 mm³ in rAdv-EGFP group), and median survival time extended from ~34 days in controls to 68 days in treated mice. These results highlight the robust antitumor efficacy of systemic rAdv-hTERTC27 delivery.
The mechanism underlying this effect likely involves dual action: direct induction of tumor cell apoptosis and activation of a potent, hTERTC27-specific immune response. Increased secretion of IL-2 and IFN-γ by activated T cells further supports enhanced immune surveillance. Notably, the use of adenoviral vectors enabled efficient delivery and sustained expression, allowing lower viral doses than previously reported, thus reducing toxicity risks.
In conclusion, rAdv-hTERTC27 represents a promising intravenous therapeutic strategy for HCC. By combining direct cytotoxicity with immune stimulation, it offers a multifaceted approach to overcoming the limitations of current treatments. Future studies should focus on optimizing dosing regimens and evaluating combination therapies to maximize clinical translation potential.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com