Production of Lipid-Nanoparticles mRNA Lung Cancer Vaccine and Neutralizing Monoclonal Antibodies to Mutated Forms of KRAS Antigens

Background: Tumour invasion is caused by mutations in the KRAS gene, and lung cancer is one of the world's leading causes of death. Aim of the study: To create monoclonal antibodies against the KRAS protein mutation in lung cancer and to produce a lipid-nanoparticle (LNP)-mRNA vaccine against various lung cancer types. Type of the study: Screening experimental study. Methodology: Using hybridoma technology, monoclonal antibodies to mutant KRAS protein were produced. The neutralising monoclonal antibodies were subsequently covalently modified to include the cell-penetrating nonapeptide arginine molecules before the antibody hinge regions. Besides, a lipid-nanoparticle-mRNA vaccine containing 10 µg mRNA of mutated forms of lung cancer KRAS protein, 10 µg mRNA of lung cancer TMEM 97 protein, and 10 µg mRNA of lung cancer TMEM 48 protein was created. To ascertain the effectiveness of the active and passive immunization of the test vaccine and monoclonal antibodies to mutant forms of the KRAS protein, animal experiments were conducted on transgenic mice implanted with lung cancer. To determine the pharmacokinetic and pharmacodynamic effects of the test vaccination in conjunction with the test monoclonal antibodies to mutant versions of the KRAS protein, immunogenicity testing was conducted in phase 1 randomised human clinical trials. Results: The protective power of monoclonal antibodies to mutant versions of lung KRAS protein and the test lung cancer LNP-mRNA vaccine was about 73% in preclinical experiments. However, it was roughly 65% in phase 1 randomised human clinical trials. In preclinical experiments, lung cancer metastasis was impeded by around 82%, whereas in phase 1 randomised human clinical trials, it was averted by 76%. Conclusion: Due to the innovative invention of active-passive immunization, which included monoclonal antibodies and the lung cancer LNP-mRNA vaccine, the current trial showed promise in preventing the spread of lung cancer.