Oncolytic virotherapy kills selectively cancer cells, leaving normal cells undamaged
The efficacy of oncolytic virotherapy is further increased by the activation of the immune system
Liver filtration and immune response against viral particles lead to poor infection of targeted tissue and limited efficacy
The VIROSHIELD™ coating technology is able to modify the behavior of oncolytic viruses, improving their therapeutic effect by different means. In particular, it has been demonstrated that the coated oncolytic adenoviruses are protected against pre-existing neutralizing antibodies, by masking their surface antigenic epitopes, while preserving their transduction capability. Moreover, a lower activation of the adaptive immune response is also observed (production of neutralizing antibodies 3-fold lower), together with a substantial decrease in liver tropism, a marked increase of tumor tropism (ratio tumor-liver 10 fold higher), and an improved blood circulation time (3-fold higher).
All these features lead to a significantly higher therapeutic efficacy when coated viruses are compared to naked ones in in vivo tumor models, especially in the presence of neutralizing antibodies. This confirms the protective role of the polymeric coating against the immune system and opens the possibility, for the first time, to treat the tumors with repeated doses of the oncolytic adenovirus without inducing a massive immune response activation and without compromising the efficacy of the treatment.
SAG-101, is a Advanced Therapy Medicinal Product (ATMP) that consists of an oncolytic adenovirus named AdNuPARmEIA, coated with a combination of two propietary oligopeptide end-modified poly(β-amino ester) polymers (VIROSHIELD™ technology) for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC).
SAG-101 is a novel, effective and safe oncolytic adenovirus that is able to replicate not only in the bulk of the tumor,
but also in pancreatic cancer stem cells (PCSC) and, more importantly, presents synergistic effects with the standard of care treatment for pancreatic tumors (i.e. gemcitabine and nab-paclitaxel). Moreover, when administered intravenously, the OM-PBAE coating of the virus is able to protect it against pre-existing neutralizing antibodies, by masking its surface antigenic epitopes, while preserving the virus transduction capability. Additionally, a lower activation of the adaptive immune response is also observed, together with a marked increase of tumor tropism, a substantial decrease in liver tropism and an improved blood circulation time.
PDAC affects one out of 8,600 males and one out of 12,300 females with a total diagnosed population worldwide of 367,000. It is the 4th most common cause of death from cancer.
Status: Proof of principle (in vivo relevant mice model with several tumour cell lines) achieved and the program has received Orphan Drug Designation in late 2017. It is expected to reach first-in-human trials (FIH) by the begining of 2021.