Targeting Mesothelin in Solid Tumours: Anti-mesothelin Antibody and Drug Conjugates

Purpose of ReviewThis review aims to summarise the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumours.Recent FindingsHigh mesothelin expression is restricted to the pericardium, pleura, peritoneum and tunica vaginalis. Mesothelin does not seem to have any normal biological function in adult normal tissues. Mesothelin is highly expressed in mesothelioma, serous ovarian cancer, pancreatic cancer and some gastric cancer and adenocarcinoma of the lung and is responsible for tumour proliferation, metastasis, resistance to chemotherapy or radiation and evasion of immune system. To date, antibody, antibody drug conjugates and bispecific antibodies with immune checkpoints have been investigated in mesothelin expressing malignancies.After a couple of decades of clinical investigation in antibody targeting mesothelin, the therapeutic benefit is relatively modest. Novel delivery of mesothelin targeting agents, more potent payload in antibody drug conjugates and immune checkpoint inhibitor, may improve therapeutic benefit.

Automated summary

This review summarises the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumors. Mesothelin is highly expressed in certain types of cancer and is responsible for tumor proliferation, metastasis, resistance to treatment, and evasion of the immune system. Various approaches, including antibodies, antibody drug conjugates, and bispecific antibodies with immune checkpoints, have been investigated for targeting mesothelin in malignancies expressing this protein.