Oncolytic adenoviruses are a promising treatment alternative for many advanced
cancers, including
colorectal cancer. However, clinical trials have demonstrated that single-agent
therapy in advanced
tumor masses is rarely curative. Poor spreading of the virus through
tumor tissue is one of the major issues limiting efficacy. As oncolytic viruses kill preferentially
cancer cells, high extracellular matrix (ECM) content constitutes potential barriers for viral penetration within
tumors. In this study, the ECM-degrading
proteases relaxin,
hyaluronidase,
elastase and
macrophage metalloelastase (
MME) were tested for their antitumor efficacy alone and in combination with oncolytic adenovirus.
MME improved the overall antitumor efficacy of oncolytic adenovirus in subcutaneous HCT116 xenografts. In a liver metastatic
colorectal cancer model, intra-tumoral treatment of primary
tumors from HT29 cells with
MME monotherapy or with oncolytic adenovirus inhibited
tumor growth. Combination
therapy showed no increased mortality in comparison with either monotherapy alone. Contradictory results of effects of
MME on
tumorigenesis and
metastasis formation have been reported in the literature. This study demonstrates for the first time in a metastatic animal model that
MME, as a monotherapy or in combination with oncolytic virus, does not increase
tumor invasiveness. Co-administration of
MME and oncolytic adenovirus may be a suitable approach for further optimization aiming at clinical applications for metastatic
colorectal cancer.