Matrix Metalloproteinases (MMPs) in Cancer Immunotherapy

Abstract

Matrix metalloproteinases (MMPs) are the zinc-dependent endopeptidases that mediate the degradation of the extracellular matrix (ECM) constituents and basement membrane to facilitate tumorigenic invasion. Reducing cell adhesion, stimulating neoangiogenesis, and inhibiting cancer cell apoptosis are the other prominent MMP-mediated subsidiary mechanisms facilitating the oncogenic processes. Further, abundant experimental and clinical evidences regarding the differential overexpression of several MMPs in various solid as well as nonsolid tumors have rendered them as potential immunotherapeutic targets against diverse cancer types. Currently, MMP-based cancer immunotherapy principally relies upon inhibition of MMP activity by either synthetic MMP inhibitors (MMPIs) or MMP-based cancer vaccines. Although the MMPIs generated considerable interest during the 1990s, they failed to sustain the expectation due to considerable side effects. Despite the initial embarrassment, now the pursuit is directed towards the development of selective and more potent inhibitors rather than the earlier broad-spectrum MMPIs along with customization of targeted delivery systems for these compounds. Alternatively, MMP-based DNA vaccines, particularly the xenogeneic vaccine strategy, have gained significant consideration in recent times due to promising response against some cancer types in preclinical models. So, this chapter elaborates about the biological functions of different MMPs in cancer, their inhibitors, and MMP-based vaccines for cancer immunotherapy as well as the challenges and future prospects.