The Immuno-Shielding protects adenoviruses from pre-existing neutralizing antibodies when delivered systemically. The efficacy of adenoviruses used as vaccines, gene therapy vectors and oncolytic viruses is often limited by the previous exposure of adenovirus in humans that leads to the development of neutralizing antibodies that inactivate adenoviruses when given intravenously. Avoiding neutralizing antibodies is necessary to reach multiple metastasis and achieve efficacious cancer treatment. An albumin-binding domain (ABD) was inserted in the adenovirus capsid in a way that when the virus is the blood, naturally occurring albumin can bind to the ABD-adenovirus and protect it from neutralizing anti-adenovirus antibodies. Scientists have recently shown that unmodified adenoviruses are completely neutralized in pre-immunized mice, whereas ABD-adenovirus can efficiently transduce tumors, show anti-tumor activity and generate immune responses to expressed proteins (Rojas LA et al., JCR, 2016). ABD technology is integrated in VCN Biosciences second therapeutic candidate VCN-11.
VCN-11 is an oncolytic adenovirus designed to evade neutralizing antibodies against adenovirus, replicate in cancer cells with dysfunctional RB1 pathway, expose tumour neoantigens of lysed tumours, improve virus tumor targeting, express hyaluronidase to enhance virus intratumoural spreading and facilitate chemotherapy and immune cells extravasation into the tumor.
Rojas LA, Condezo GN, Moreno R, Fajardo CA, Arias-Badia M, San Martín C, Alemany R. Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery. J Control Release. 2016 Sep 10;237:78-88. doi: 10.1016/j.jconrel.2016.07.004. Epub 2016 Jul 4.