Enhancement of the oncolytic potency of conditionally replicative adenoviruses

Enhancement of the oncolytic potency of conditionally replicative adenoviruses

W. Dong1, K.Y. Au1, A. Gros2, J.W.G. van Ginkel1, M. Cascallo2, W.R. Gerritsen3, R. Alemany2, J.J.M. Meulenberg1, V.W. van Beusechem1,3
1ORCA Therapeutics, Amsterdam, The Netherlands; 2Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, Barcelona, Spain; and 3Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.

Oncolytic adenoviruses represent a novel class of anticancer agents, designed to selectively replicate in tumor cells and to destroy these cells by inducing lysis (oncolysis). We have generated ORCA-010, a new oncolytic adenovirus based on ORCA's proprietary T1 technology, which refers to a specific mutation in the E3 gp19K gene. This mutation results in enhanced potency in human tumours and in enhanced anti-tumoural activity when injected intratumourally in different models in vivo. The virus furthermore contains the E1A-Delta24 mutation for cancer-selective replication and a fiber-RGD mutation for efficient infection of cancer cells. We evaluated the oncolytic potency of ORCA-010 on a broad panel of different human cancer cell lines and found that this virus is profoundly more potent in killing cancer cells than previously developed oncolytic adenoviruses. Upon intratumoural injection of ORCA-010 into subcutaneous human prostate, ovary and lung cancer tumour xenografts in nude mice we observed tumour growth inhibition and prolonged survival of the animals. We are currently developing ORCA-010 for clinical testing in a Phase I/II trial in patients with locally advanced prostate cancer.