Kumar Shashank, Shuaib Mohd, Prajapati Kumari Sunita, Singh Atul Kumar, Choudhary Princy, Singh Sangeeta, Gupta Sanjay
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab 151401 India.
Applied Science Department, Indian Institute of Information Technology, Allahabad, Uttar Pradesh 211012 India.
3 Biotech. 2022 Mar;12(3):72. doi: 10.1007/s13205-022-03140-3. Epub 2022 Feb 20.
Triple-negative breast cancer (TNBC) is an aggressive, metastatic/invasive sub-class of breast cancer (BCa). Cell surface protein-derived multi-epitope vaccine-mediated targeting of TNBC cells could be a better strategy against the disease. Literature-based identified potential cell surface markers for TNBC cells were subjected to expression pattern and survival analysis in BCa patient sample using TCGA database. The cytotoxic and helper T-lymphocytes antigenic epitopes in the test proteins were identified, selected and fused together with the appropriate linkers and an adjuvant, to construct the multi-epitope vaccine (MEV). The immune profile, physiochemical property (PP) and world population coverage of the MEV was studied. Immune simulation, cloning in a suitable vector, molecular docking (against Toll-like receptors, MHC (I/II) molecules), and molecular dynamics simulations of the MEV was performed. Cell surface markers were differentially expressed in TNBC samples and showed poor survival in TNBC patients. Satisfactory PP and WPC (up to 89 and 99%) was observed. MEV significant stable binding with the immune molecules and induced the immune cells in silico. The designed vaccine has capability to elicit immune response which could be utilized to target TNBC alone/combination with other therapy. The experimental studies are required to check the efficacy of the vaccine.
The online version contains supplementary material available at 10.1007/s13205-022-03140-3.
三阴性乳腺癌（TNBC）是乳腺癌（BCa）中一种侵袭性、转移性/浸润性亚类。基于细胞表面蛋白的多表位疫苗介导的TNBC细胞靶向可能是对抗该疾病的更好策略。利用TCGA数据库，对基于文献确定的TNBC细胞潜在细胞表面标志物在BCa患者样本中进行表达模式和生存分析。鉴定、选择测试蛋白中的细胞毒性和辅助性T淋巴细胞抗原表位，并与合适的接头和佐剂融合在一起，构建多表位疫苗（MEV）。研究了MEV的免疫概况、理化性质（PP）和世界人口覆盖率。对MEV进行了免疫模拟、在合适载体中的克隆、分子对接（针对Toll样受体、MHC（I/II）分子）以及分子动力学模拟。细胞表面标志物在TNBC样本中差异表达，且在TNBC患者中显示出生存率较差。观察到令人满意的PP和WPC（分别高达89%和99%）。MEV与免疫分子有显著稳定的结合，并在计算机模拟中诱导免疫细胞。设计的疫苗有能力引发免疫反应，可单独用于靶向TNBC或与其他疗法联合使用。需要进行实验研究来检验疫苗的疗效。
在线版本包含可在10.1007/s13205-022-03140-3获取的补充材料。
