Immunotherapy Targeting Heparanase-1 May Be the Dawn of Cancer Sufferers

Although there have been great advances in preventive andtherapeutic approaches, malignant tumor is still one of the majorcauses of death in the world. The control of invasion and metastasisof advanced-stage malignancies remains the pain in the neck.Recently, cancer immunotherapy has emerged as a new supplementfor cancer treatment that has weak side effects and favorableapplicability. Antigen presentation is critical for triggering suchimmune response, and Dendritic cells and Cytotoxic T Lymphocytesare very important in this process. Although cancer immunotherapyhas shown encouraging results in some human clinical trials, therehave been some momentous setbacks: (1) Most Tumor AssociatedAntigens (TAAs) that have been described are either tissue specificor nonsignificant for cell survival; (2) the poor reactivity of T cellsagainst TAAs; (3) immunosuppressive features of tumor cells; and(4) the expansion of Treg cells. Therefore, it is critical to identifypromising TAAs for tumor immunotherapy, and a class of TAAtermed ‘Universal Tumor Antigens’ has been proposed that issupposed not only to induce antitumor immunity against most tumortypes, but also to have crucial functional roles in tumor growthand development. Heparanase-1 can degrade the heparan sulfateproteoglycans in the extracellular matrix and basement membrane.Unlike most other TAA, heparanase-1 is found highly expressedin most mammalian malignant tumors, and many hurdles could beovercome when cancer immunotherapy is targeting heparanase-1.It was demonstrated many years ago that the metastatic potential oftumor cells is correlated with heparanase-1 expression. Thereby, itcan be hypothesized that heparanase-1 is a key enzyme involved inthe metastasis of malignant tumors, and immunotherapy aiming atheparanase-1 may be the dawn of advanced-stage cancer sufferers.