Medical application of the monoclonal antibody SKM9-2 against sialylated HEG1, a new precision marker for malignant mesothelioma

Proceedings of the Japan Academy 2023 [Link]

Shoutaro Tsuji, Kohzoh Imai

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleural cavity. Pathologically distinguishing MPM from other pleural lesions is often difficult. We searched for marker antigens to facilitate the pathological diagnosis of MPM and found useful markers for the pathological detection of malignant mesothelioma. Among them, the anti-mesothelioma monoclonal antibody SKM9-2, which was isolated as a clone binding to specimens of MPM (but not to specimens of lung adenocarcinoma) by immunohistochemical screening, showed higher specificity and sensitivity than traditional mesothelioma markers. SKM9-2 recognizes both sialylated O-glycans and peptide sequences in HEG1, and its glycan modifications are specific to mesothelioma. New effective treatments for MPM are needed because the prognosis of patients with MPM is usually poor. SKM9-2 can be used as a seed for next-generation antibody drugs with strong cytotoxic activities. In this review, we have summarized our research on antibody development for MPM diagnosis and treatment.