Amity Institute of Microbial Technology, Amity University Uttar Pradesh, Noida, India.
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
Immunol Res. 2023 Dec;71(6):909-928. doi: 10.1007/s12026-023-09404-1. Epub 2023 Jul 6.
Small cell lung cancer (SCLC) is one of the most common cancers and it is the sixth common cause for cancer-related deaths. The high plasticity and metastasis have been a major challenge for humanity to treat the disease. Hence, a vaccine for SCLC has become an urgent need of the hour due to public health concern. Implementation of immunoinformatics technique is one of the best way to find a suitable vaccine candidate. Immunoinformatics tools can be used to overcome the limitations and difficulties of traditional vaccinological techniques. Multi-epitope cancer vaccines have become a next-generation technique in vaccinology which can be used to stimulate more potent immune response against a particular antigen by eliminating undesirable molecules. In this study, we used multiple computational and immunoinformatics approach to design a novel multi-epitope vaccine for small cell lung cancer. Nucleolar protein 4 (NOL4) is an autologous cancer-testis antigen overexpressed in SCLC cells. Seventy-five percent humoral immunity have been identified for this particular antigen. In this study, we mapped immunogenic cytotoxic T lymphocyte, helper T lymphocyte, and interferon-gamma epitopes present in NOL4 antigen and designed a multi-epitope-based vaccine using the predicted epitopes. The designed vaccine was antigenic, non-allergenic, and non-toxic with 100% applicability on human population. The chimeric vaccine construct showed stable and significant interaction with endosomal and plasmalemmal toll-like receptors in molecular docking and protein-peptide interaction analysis, thus assuring a strong potent immune response against the vaccine upon administration. Therefore, these preliminary results can be used to carry out further experimental investigations.
小细胞肺癌（SCLC）是最常见的癌症之一，也是癌症相关死亡的第六大常见原因。高可塑性和转移已经成为人类治疗这种疾病的主要挑战。因此，由于公共卫生的关注，SCLC 的疫苗已成为当务之急。免疫信息学技术的实施是寻找合适疫苗候选物的最佳方法之一。免疫信息学工具可用于克服传统疫苗技术的局限性和困难。多表位癌症疫苗已成为疫苗学中的下一代技术，可通过消除不良分子来刺激针对特定抗原的更有效免疫反应。在这项研究中，我们使用了多种计算和免疫信息学方法来设计一种用于小细胞肺癌的新型多表位疫苗。核仁蛋白 4（NOL4）是一种在 SCLC 细胞中过度表达的自体癌症睾丸抗原。已经鉴定出针对该特定抗原的 75%的体液免疫。在这项研究中，我们对 NOL4 抗原中存在的免疫原性细胞毒性 T 淋巴细胞、辅助 T 淋巴细胞和干扰素-γ表位进行了定位，并使用预测的表位设计了一种多表位疫苗。设计的疫苗具有抗原性、非变应原性和无毒副作用，在人类中的适用性为 100%。嵌合疫苗构建体在分子对接和蛋白-肽相互作用分析中显示出与内体和质膜 Toll 样受体的稳定和显著相互作用，从而确保在给药后对疫苗产生强烈有效的免疫反应。因此，这些初步结果可用于进一步的实验研究。
