Oncolytic Virus Expressing Angiostatic Factors under an Immediate Early Viral Promoter
T2007-142 Tumor-targeting oncolytic virus is able to kill cancer cells while sparing normal cells and encodes anti-angiogenic factors that reduced blood vessel formation and may modulate innate immune response.
Glioblastoma is the most common primary malignant brain tumor, with a median survival of less than 15 months from diagnosis. Current standard of care combines surgical resection, with radiation and chemotherapy. However, many patients recur with resistant tumors that require alternative treatments that circumvent therapeutic resistance. The tumor microenvironment is increasingly recognized as an important determinant not just for tumor progression but also for effective believe of therapeutics. Recent studies have revealed that treatment strategies aimed at treating just cancer cells or their environment alone are not effective. An oncolytic virus (OV) is needed to maximize expression of the therapeutic transgene, giving it the power to destroy cancer cells by its tumor specific replication potential and target tumor vasculature to enhance therapeutic efficacy.
Dr. Kaur and her team at The Ohio State University have developed a tumor-targeting oncolytic viral therapy derived from herpes simplex virus. This oncolytic virus (OV) is able to target and kill tumor cells while sparing normal cells. Furthermore, it expresses an anti-angiogenic secreted protein which can block new blood vessel formation in the tumor, and also been reported to have immunomodulatory properties. Pre-clinical evaluation of her OV, called RAMBO (Rapid Anti-Angiogenesis Mediated By Oncolytic Virus), has shown promise. OV therapy with RAMBO in mouse models of glioblastoma results in prolonged survival compared to OV that lack expression of the anti-angiogenic protein. The RAMBO virus has completed pre-clinical safety and efficacy studies in mice, and is ready to be evaluated in higher-level mammals.
- Solid cancer therapeutics
- Uses an oncolytic virus that expresses a recombinant bacterial enzyme
- Secretes large amount of glycosidase to enhance the spread of the molecule through tumor cells
- Uses Choindroitinase ABC to allow the spread of large therapeutic or imaging molecules