Aali Faranak, Doosti Abbas, Shakhsi-Niaei Mostafa
Department of Biology, ShK.C., Islamic Azad University, Shahrekord, Iran.
Biotechnology Research Center, ShK.C., Islamic Azad University, Shahrekord, Iran.
Sci Rep. 2025 Jun 5;15(1):19774. doi: 10.1038/s41598-025-04089-y.
Breast cancer (BC) is one of the most common cancers among women, with its prevalence exhibiting a troubling increase. Increased emphasis must be made on developing effective therapies owing to the high prevalence and increasing incidence of breast cancer. Presently, traditional passive therapies have several unresolved limitations. Conversely, novel immunotherapy strategies, such as cancer vaccines, have shown encouraging potential in addressing late stages of breast cancer. The primary aim of this work was to use MAGE-A, MAM-A, and Gal-3 antigenic proteins in the formulation of a multiepitope vaccine for breast cancer. To elicit strong immune responses, we first discovered antigenic epitopes of proteins and evaluated their immunogenicity. To diminish junctional immunogenicity, promiscuous epitopes were conjugated with the appropriate adjuvant (IL-12 protein) and linked with a suitable linker (GSST). The optimal estimated a three-dimensional model was enhanced and verified to get a superior 3D model. Molecular docking studies and dynamic modeling were used to establish the structural stability and integrity of the vaccine/mouse TLR-2, 4, 7, and 9 complexes. The vaccine was finally optimized and cloned into pcDNA3.1(+) vector. Moreover, the immunological simulation of the vaccine demonstrated its capacity to elicit immune responses (B cells, T cells, antibodies, and cytokines) against breast cancer. Consequently, the examination of the developed vaccine by immunoinformatic demonstrates its potential to provoke strong humoral and cellular immune responses in the intended organism. Consequently, it has potential as a therapeutic agent against breast cancer and may facilitate more study in the domain.
乳腺癌（BC）是女性中最常见的癌症之一，其患病率呈令人担忧的上升趋势。由于乳腺癌的高患病率和不断上升的发病率，必须更加重视开发有效的治疗方法。目前，传统的被动疗法存在一些尚未解决的局限性。相反，新型免疫疗法策略，如癌症疫苗，在治疗乳腺癌晚期方面显示出令人鼓舞的潜力。这项工作的主要目的是在乳腺癌多表位疫苗的配方中使用黑色素瘤相关抗原A（MAGE - A）、黑色素瘤相关抗原MAM - A和半乳糖凝集素 - 3（Gal - 3）抗原蛋白。为了引发强烈的免疫反应，我们首先发现了蛋白质的抗原表位并评估了它们的免疫原性。为了降低连接免疫原性，将混杂表位与合适的佐剂（白细胞介素 - 12蛋白）偶联，并与合适的连接子（GSST）相连。对优化后的三维模型进行增强和验证，以获得更优的三维模型。利用分子对接研究和动力学建模来确定疫苗与小鼠Toll样受体2、4、7和9复合物的结构稳定性和完整性。最终对疫苗进行优化并克隆到pcDNA3.1(+)载体中。此外，疫苗的免疫模拟显示了其引发针对乳腺癌的免疫反应（B细胞、T细胞、抗体和细胞因子）的能力。因此，通过免疫信息学对所开发疫苗的检测表明，它有潜力在目标生物体中引发强烈的体液免疫和细胞免疫反应。因此，它有作为乳腺癌治疗剂的潜力，并可能促进该领域的更多研究。
