Revolutionizing NSCLC Treatment: Exploring the Potential of In Silico-designed Multiepitope Vaccines

Non-Small Cell Lung Cancer (NSCLC) presents a formidable challenge in oncology,necessitating innovative strategies for improved therapeutic outcomes [۱]. This study explores cuttingedgeimmunotherapy, focusing on the potential of in silico-designed multiepitope vaccines to reshapeNSCLC treatment. Four NSCLC-associated antigensVimentin, PRAME, TXNDC۵, and AKAP۴ wereretrieved from the NCBI database. B cell prediction involved ABCpred, while T cell CD۸+ predictionsused NetCTL ۱.۲ and IEDB servers, and CD۴+ predictions employed NetMHCIIpan-۴.۰. Subsequently,comprehensive analyses, including validation, allergenicity, toxicity, and physicochemical assessments,were performed via web servers. Employing AAY, GPGPG, and KFER as linkers, and HBHA and CpGOligonucleotides(ODNs) as adjuvants linked by EAAAK, the final construct underwent disulfideengineering, molecular docking, immune simulation, and codon adaptation for effective vaccineproduction. Identifying ۸ linear B-cell epitopes and ۱۶ and ۱۰ epitopes for CD۴+ and CD۸+ cells,respectively, the predicted epitopes were linked to facilitate proper protein folding. No allergenicity wasobserved, and the vaccine exhibited proper antigenicity (۰.۷۲۶۷۲۲). Molecular docking studiessuggested a high affinity for human receptors. Codon optimization and in silico cloning into the E. coliK۱۲ strain indicated potential for expression, with a CAI of ۱.۰ and GC parameters of ۵۲.۸۲. Notably,most current NSCLC vaccines lack efficacy, especially in targeting all three crucial oncoproteins. Ournovel vaccine shows promise and uniqueness, emphasizing the need for continued research to ensurecomprehensive evaluation in human subjects. The vaccine, utilizing antigens found in CAR T-celltreatments, is designed for combination use, potentially amplifying inflammatory factors and enhancingCAR T-cell effectiveness [۲].

کلیدواژه ها:

NSCLC ، Multiepitope vaccine ، in silico design ، Immunotherapy