Current and Emerging Therapy for Malignant Pleural Mesothelioma: Focus on CD26/Dipeptidyl Peptidase IV as a Therapeutic Target

BACKGROUND: Malignant mesothelioma is a largely incurable disease that is refractory to current therapies. CD26 is a multifunctional cell surface protein involved in autoimmune disease, diabetes, and cancer. It has a role in T cell function, extracellu-lar protein modification, as a prognostic factor for cancer, and as a therapeutic target for malignant mesothelioma. New treatment strategies are urgently needed for malig-nant pleural mesothelioma (MPM), and CD26-targeted therapy represents a novel ap-proach. OUTLINE: In this review, the most current and up-to-date literature available was reviewed and the current state of malignant mesothelioma treatment is described. Throughout the review the need for new therapeutic approaches is highlighted in the shortcomings of current therapy. CD26 is a target that is fit to take on these shortcom-ings. In this review we discuss the structure and function of CD26, its role in malignant mesothelioma and the future of anti-CD26 therapy as a versatile immunotherapeutic option. CONCLUSION: This review highlights the areas of most promise in treating MPM, these in-clude immune checkpoint blockade, passive immunization, and based on our recently published data, targeting of CD26 with its specific mAb. Finally we describe how the an-ti-CD26 mAb YS110 was recently evaluated in the first-in-human phase I clinical trial, showing prolonged disease stabilization and a favorable side effect profile. Through better understanding of CD26, new pathways to treating and potentially curing malig-nant mesothelioma may be discovered.