Mucin 13 and Mesothelin (MUC13 and MSLN)

Mucin 13 (MUC13) and Mesothelin (MSLN) are distinct cell surface glycoproteins frequently overexpressed in epithelial malignancies such as colorectal, pancreatic, and ovarian cancers [1, 4, 11]. MUC13 is a transmembrane mucin involved in cell signaling and survival pathways, including HER2 and YAP1 activation [3, 10], while MSLN is a GPI-anchored protein that facilitates cell adhesion through its interaction with MUC16 (CA125) [4, 7]. The combination of MUC13 and MSLN is being developed as a dual-target pair for next-generation immunotherapies, such as AND-gated T-cell engagers (TCEs) and bispecific CAR-T cells, to enhance tumor specificity and mitigate "on-target, off-tumor" toxicities [11, 18]. While individual MSLN-targeted therapies, such as Anetumab ravtansine and Gavo-cel, have shown clinical activity, they are often limited by toxicities in normal tissues like the pleura and lungs [11, 12, 14]. Consequently, the co-expression of MUC13 and MSLN in specific tumor types like colorectal cancer offers a unique therapeutic window for precision oncology [11].

Other names

DRCC1Down-regulated in colon cancer 1MPFMegakaryocyte-potentiating factorSMRPSoluble mesothelin-related proteinCAK1

Antibody-drug conjugation (ADC) for intracellular toxin delivery, chimeric antigen receptor (CAR) T-cell activation for direct tumor lysis, and AND-gated T-cell engagement for dual-antigen dependent cytotoxicity [11, 12, 14].