An oncolytic AdV vector expressing relaxin in combination with immune modulators (oAd/IL-12/GM-RLX) was demonstrated to degrade the ECM, enhance penetration of mAB therapeutics and promote durable antitumor responses in models of pancreatic cancer.77 Oncolytic AdV expressing PH20 hyaluronidase demonstrated hyaluronan destruction in the ECM that facilitated OV dissemination.78 Importantly, this treatment left the protein matrix of the TME intact, thus while OV penetration was facilitated, metastasis of tumor cells from the tumor was not. This evidence concerns the gene SPAM1 and neoplasm.