A Cell-Specific Nuclear Factor-Kappa B–Activating Gene Expression Strategy for Delivering Cancer Immunotherapy

In recent years, new immunotherapies have greatly contributed to the success of cancer treatment. However, cancer cell-specific antigens limit the effectiveness of these immunotherapies. Identification of neoantigens through tumor sequencing and bioinformatics may help advance research into personalized cancer vaccines. This study evaluated a new immunotherapy by developing a cancer cell-specific gene expression technique that uses a nuclear factor-kappa B (NF-κB)-activating gene expression vector to express a protein or peptide on the surface of cancer cells. These proteins or peptides function as an artificial neoantigen to stimulate the immune system to kill cancer cells. The study demonstrated that NF-κB RelA was widely over-activated only in cancer cells. It also showed that a NF-κB-activating gene expression (Nage) vector, which consisted of a NF-κB-specific promoter (DMP) prepared by fusing a NF-κB decoy sequence to a minimal promoter and a downstream effector gene, could specifically express a protein or peptide on the surface of various cancer cells. By packaging the Nage vector in an adeno-associated virus, in vivo tumors can be significantly inhibited or even eradicated via intravenously injected recombinant adeno-associated viruses.