Substance P 神经肽 神经递质/神经调节剂|CAS 33507-63-0

Abstract

Esophageal squamous cell carcinoma (ESCC) has limited treatment options post-immune checkpoint inhibitor (ICI) resistance. We developed IPM514, a universal multi-epitope mRNA lipid nanoparticle (LNP) vaccine targeting tumor-associated antigens identified via transcriptomic analysis of TCGA/GTEx datasets and validated in 132 ESCC patients. IPM514 contains 15 fragments from 9 antigens, covering most patients and over half of HLA subtypes. Peripheral blood mononuclear cells (PBMCs) from healthy donors and ESCC patients stimulated with IPM514 effectively expanded specific T cells that exhibited significant cytotoxic activity against ESCC and other squamous cell carcinomas with similar antigen profiles. In HLA-transgenic mouse models, IPM514 suppressed tumor growth, extended survival, and provided durable protection. Importantly, combination therapy with PD-1 blockade augmented antitumor efficacy by promoting immune cell infiltration, upregulating antigen presentation pathways, and reprogramming the tumor microenvironment toward an anti-tumorigenic state. These results demonstrate IPM514 represents a promising novel mRNA vaccine strategy for improving ESCC immunotherapy.