Novel Ovarian Cancer Therapy
Abstract
Owing to their exciting potential, virotherapy agents have been rapidly applied as experimental therapy for cancer of the ovary. In addition toaddressing safety and efficacy, these recent human trials have also define the barriers to optimized virotherapy effectiveness. Specifically, these human trials have highlighted two key barriers limiting the full effectiveness of current virotherapy approaches for cancer of the ovary.First, pre-formed immunity to the virotherapy viral agent, in the form of antibodies, could neutralize the administered agent. This is highlyrelevant as many virotherapy agents are based on viruses to which humans have commonly been exposed. For example, the common coldvirus, termed adenovirus, has been highly useful as a virotherapy agent, however its use would be potentially impacted by the presence ofantibodies to human adenovirus in treated subjects. We were able to construct an ovarian cancer CRAd with a SPARC promoter for tumorselective replication. Initially, we proposed a gorilla adenovirus base but found that a human adenovirus 5 base provided some technicaladvantages. In addition, we were able to show the SPARC-controlled CRAd replication in human and murine ovarian cancer cells selectively and induced direct tumor cell oncolysis. We were also able to show that the targeted CRAd could accomplish tumor cell oncolysis in anorthotopic challenge model. However, in pilot studies to this point, we have not been able to exploit this latter capacity to induce systemicimmunity. After establishing proof-of-principle, we will shift to simian 36 base which can be modified as readily as human adenoviruses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1126838
Entities
People
- David T. Curiel
Organizations
- Washington University in St. Louis