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Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate Cancer: An In Silico Approach.
Cell Biochemistry and Biophysics ( IF 1.8 ) Pub Date : 2020-04-28 , DOI: 10.1007/s12013-020-00912-7
Prasanta Patra 1 , Manojit Bhattacharya 1, 2 , Ashish Ranjan Sharma 2 , Pratik Ghosh 1 , Garima Sharma 3 , Bidhan Chandra Patra 1 , Bidyut Mallick 4 , Sang-Soo Lee 2 , Chiranjib Chakraborty 2, 5
Affiliation  

Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a vaccine element by (GGGGS)3 peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the vaccine element and HLA class I antigen with the low ACE value of −251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases peptide vaccine molecule will be an effective candidate for the treatment of the PCa.



中文翻译:


抗前列腺癌的下一代多表位碱肽候选疫苗的鉴定和设计:计算机方法。



前列腺癌 (PCa) 是男性第二大诊断癌症,在总体癌症诊断中排名第五。在过去的几十年里,它已成为老年男性中一种严重威胁生命的疾病。在疾病早期,当疾病呈局部形式时,可采用放射和手术治疗来对抗这种疾病。在出现不良情况时,雄激素剥夺疗法、化疗、激素疗法等被广泛用作治疗手段。然而,研究发现应用这些疗法后会出现一些副作用。在当前的工作中,应用了多种免疫信息技术从过度表达的 PCa 抗原蛋白中配制多表位疫苗。经过多种计算机工具验证后,从五种前列腺抗原蛋白(PSA、PSMA、PSCA、STEAP 和 PAP)中鉴定出总共 13 个表位。这些表位通过 (GGGGS) 3肽接头融合形成疫苗元件。随后,5, 6-二甲基呫吨酮-4-乙酸 (DMXAA) 被用作佐剂来启动和诱导 STING 介导的细胞毒性级联反应。此外,疫苗元件与HLA I类抗原进行分子对接,ACE值较低,为-251 kcal/mol,显示出显着的结合。使用正态模式分析 (NMA) 的分子模拟表明对接复合物是一种稳定的复合物。因此,这一观察强烈表明我们的多表位碱基肽疫苗分子将成为治疗前列腺癌的有效候选分子。

更新日期:2020-04-28
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