Pancreatic ductal adenocarcinoma tumor-associated antigens and neoantigens (PDAC TAAs/Neoantigens)

Pancreatic ductal adenocarcinoma (PDAC) tumor-associated antigens (TAAs) and neoantigens represent a heterogeneous group of molecular targets used in immunotherapy to treat pancreatic cancer (PubMed: 31510749). TAAs are self-proteins that are abnormally expressed in tumors, such as Mesothelin (MSLN), Mucin 1 (MUC1), and Carcinoembryonic Antigen (CEA), while neoantigens are novel peptides resulting from non-synonymous somatic mutations in genes like KRAS, TP53, and SMAD4 (NIH: PMC7355463). These targets are exploited by various therapeutic modalities, including peptide vaccines, dendritic cell vaccines, and adoptive cell transfers like CAR-T or TCR-T therapies. The primary biological role of these antigens in a therapeutic context is to serve as flags for the immune system, specifically CD8+ and CD4+ T-cells, to identify and destroy malignant cells. However, PDAC presents a unique challenge due to its low mutational burden and a highly immunosuppressive, desmoplastic stroma that hinders T-cell infiltration and activity (Nature: 10.1038/s41586-023-06063-y). Clinical trials are currently investigating personalized neoantigen vaccines and combinations with checkpoint inhibitors to overcome these barriers and improve patient outcomes.

Other names

PDAC antigensPancreatic cancer neoantigensTumor-specific antigensTAAsNeoantigens

Stimulation of the host immune system to recognize and eliminate cancer cells through the presentation of tumor-specific or tumor-associated peptides to T-cells, often via vaccines or adoptive cell transfer.