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Mesothelin is a surface protein on mesothelioma, ovarian, and pancreatic cancers, targeted by ADCs, CAR-T, and T-cell engagers.
Mesothelin (MSLN) is a GPI-anchored protein with restricted normal expression on mesothelial surfaces; it binds MUC16/CA-125 but its function is largely dispensable, so targeting it carries little on-target risk in healthy tissue. It is expressed in 85-100% of epithelioid mesothelioma (lower in sarcomatoid), 80-90% of pancreatic cancer, 60-70% of serous ovarian cancer, and lung adenocarcinoma. Anetumab ravtansine failed in mesothelioma, which set back the ADC route. Mesothelin remains a leading solid-tumour CAR-T target, including regionally delivered and mRNA-CAR approaches designed to overcome poor infiltration and short persistence, and T-cell engagers are also in development. The simple version is a surface protein shared by several hard-to-treat cancers that engineered immune cells can be aimed at.
In plain words · Mesothelin is a surface protein on mesothelioma, ovarian, and pancreatic cancers, targeted by ADCs, CAR-T, and T-cell engagers.
Mesothelin is a surface protein on mesothelioma, ovarian, and pancreatic cancers, targeted by ADCs, CAR-T, and T-cell engagers.
Binds MUC16/CA-125; function largely dispensable.
2 products aim at Mesothelin: antibody-drug conjugates and bispecific antibodies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Tumour-associated overexpression: 2 cell-killing or cell-finding medicines (EB-MF-CAR-NK-01, Anetumab ravtansine) aim at the antigen, which HPA finds stained high in 4 normal tissues; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA MSLN: RNA tissue enhanced (adipose tissue 89 nTPM, fallopian tube 262 nTPM); blood lineage group enriched (dendritic cells 6 nTPM, monocytes 2 nTPM); high antibody staining in 4 normal tissues; highest cancer staining pancreatic cancer (4 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Mesothelioma, Pancreatic ductal adenocarcinoma, Ovarian cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas MSLN tissue; Human Protein Atlas MSLN pathology; Open Targets ENSG00000102854 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Yamaguchi et al, J. Biol. Chem, 1994, "A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5". Source.
Binds MUC16/CA-125; function largely dispensable.
RNA: tissue enhanced (adipose tissue 89 nTPM, fallopian tube 262 nTPM), detected in many normal tissues. Blood: group enriched (dendritic cells 6 nTPM, monocytes 2 nTPM).
Medium: Colon, Endometrium, Nasopharynx, Rectum.
RNA cancer enhanced: Lung Adenocarcinoma 473 pTPM, Ovary Serous Cystadenocarcinoma 671 pTPM.
Medium only: cervical cancer, liver cancer, lung cancer, testis cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Mesothelioma | 85-100% | Epithelioid histology | Lower in sarcomatoid | Wikipedia |
| Pancreatic ductal adenocarcinoma | 80-90% | IHC, any expression | Wikipedia | |
| Ovarian cancer | 60-70% | IHC, any expression | Serous | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Anetumab ravtansine was the first antibody-drug conjugate tested in a randomised trial in mesothelioma, aimed at the mesothelin protein that nearly all mesotheliomas carry; it was no better than vinorelbine chemotherapy as second-line treatment, and is now being tried with pembrolizumab.
EB-MF-CAR-NK-01 is an experimental bispecific antibody from Beijing Biotech in phase 2 trials for mesothelioma, aimed at Mesothelin and FAP.
Query for this target: (TITLE:"Mesothelin" OR ABSTRACT:"Mesothelin" OR TITLE:"MSLN" OR ABSTRACT:"MSLN") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Mesothelin, not a curated reading list.
Shares NCI Center for Cancer Research (intramural programme) and the tags car-t-target, adc-target.
Shares Metastatic pancreatic ductal adenocarcinoma, CAR-T cell therapy, Pancreatic ductal adenocarcinoma and the tags car-t-target, adc-target.
Shares Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16), MUC16 (CA-125), Ovarian cancer and the tag adc-target.
Shares Ovarian cancer and the tag adc-target.
Shares CAR-T cell therapy and the tag car-t-target.
Shares CAR-T cell therapy and the tag car-t-target.
Shares Pancreatic ductal adenocarcinoma and the tag adc-target.
Shares CAR-T cell therapy and the tag car-t-target.