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

Jun Zhang, Dai Ming Fan, Jian Min Yang


Although there have been great advances in preventive and therapeutic approaches, malignant tumor is still one of the major causes of death in the world. The control of invasion and metastasis of advanced-stage malignancies remains the pain in the neck. Recently, cancer immunotherapy has emerged as a new supplement for cancer treatment that has weak side effects and favorable applicability. Antigen presentation is critical for triggering such immune response, and Dendritic cells and Cytotoxic T Lymphocytes are very important in this process. Although cancer immunotherapy has shown encouraging results in some human clinical trials, there have been some momentous setbacks: (1) Most Tumor Associated Antigens (TAAs) that have been described are either tissue specific or nonsignificant for cell survival; (2) the poor reactivity of T cells against TAAs; (3) immunosuppressive features of tumor cells; and (4) the expansion of Treg cells. Therefore, it is critical to identify promising TAAs for tumor immunotherapy, and a class of TAA termed 'Universal Tumor Antigens' has been proposed that is supposed not only to induce antitumor immunity against most tumor types, but also to have crucial functional roles in tumor growth and development. Heparanase-1 can degrade the heparan sulfate proteoglycans in the extracellular matrix and basement membrane. Unlike most other TAA, heparanase-1 is found highly expressed in most mammalian malignant tumors, and many hurdles could be overcome when cancer immunotherapy is targeting heparanase-1. It was demonstrated many years ago that the metastatic potential of tumor cells is correlated with heparanase-1 expression. Thereby, it can be hypothesized that heparanase-1 is a key enzyme involved in the metastasis of malignant tumors, and immunotherapy aiming at heparanase-1 may be the dawn of advanced-stage cancer sufferers.

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