de Omena Neta Genilda Castro, da Silva Junior Jose Wilson Batista, Rocha Rodger Marcel Lima, da Silva Fernandes Duarte Ana Kelly, Gomes Emisael Stenio Batista, Zanchi Fernando Berton, de Sales Marques Carolinne, de Carvalho Fraga Carlos Alberto
Federal University of Alagoas, Arapiraca, Alagoas, Brazil.
Federal Institute of Alagoas, Satuba, Alagoas, Brazil.
Cell Biochem Biophys. 2025 Aug 13. doi: 10.1007/s12013-025-01830-2.
The increase in cancer incidence and mortality demonstrates the need for more effective anti-tumor therapies. Targeted therapies, such as cancer testicular antigens (CTAs), are promising as they are expressed in tumor cells but not in normal cells. TFDP3, a CTA expressed in cancers such as triple-negative breast cancer, prostate cancer, childhood T-cell lymphoblastic leukemia, and hepatocellular carcinoma, was chosen as a target for vaccine development. This study aimed to predict a multi-epitope vaccine based on TFDP3 using immunoinformatics tools to identify antigenic epitopes that interact with B lymphocytes, CD4+T lymphocytes, and CD8+T lymphocytes. Three epitopes from each lymphocyte type were selected, considering factors such as antigenicity, allergenicity, toxicity, IFN-γ induction, and population coverage. The vaccine also included adjuvants and ligands that ensure the stability and proper processing of the epitopes. The in-silico analysis revealed that the vaccine has favorable physicochemical properties, low homology with human proteins, and interactions with Toll-like receptors, ensuring stability. The population coverage world of the MHC class I and II epitopes were 93.55%. Additionally, the vaccine can be cloned and induce a robust immune response after three administrations. Despite the promising results, immunotherapy still faces challenges, such as tumor heterogeneity and immune evasion. In vitro and in vivo studies are necessary to assess the vaccine's efficacy and safety for future cancer treatments that express TFDP3.
癌症发病率和死亡率的上升表明需要更有效的抗肿瘤疗法。靶向疗法，如癌睾丸抗原（CTA），很有前景，因为它们在肿瘤细胞中表达而不在正常细胞中表达。TFDP3是一种在三阴性乳腺癌、前列腺癌、儿童T细胞淋巴细胞白血病和肝细胞癌等癌症中表达的CTA，被选为疫苗开发的靶点。本研究旨在利用免疫信息学工具基于TFDP3预测一种多表位疫苗，以识别与B淋巴细胞、CD4+T淋巴细胞和CD8+T淋巴细胞相互作用的抗原表位。考虑到抗原性、致敏性、毒性、IFN-γ诱导和人群覆盖率等因素，从每种淋巴细胞类型中选择了三个表位。该疫苗还包括确保表位稳定性和正确加工的佐剂和配体。计算机模拟分析表明，该疫苗具有良好的物理化学性质，与人蛋白质的同源性低，并且与Toll样受体相互作用，确保了稳定性。MHC I类和II类表位的全球人群覆盖率为93.55%。此外，该疫苗可以克隆，并在三次给药后诱导强烈的免疫反应。尽管结果很有前景，但免疫疗法仍然面临挑战，如肿瘤异质性和免疫逃逸。有必要进行体外和体内研究，以评估该疫苗在未来治疗表达TFDP3的癌症时的疗效和安全性。
