| Synergistic effects of immune cell-viral biotherapy in the treatment of cancer
One of the major limitations of using replication-restricted (oncolytic) viruses in the treatment of cancer is the difficulty in delivering these agents to the tumor and so most clinical trials with these agents rely on intratumoral injection. We had been working with a population of immune cells, called CIK cells, that have NK and T cell phenotypic markers and were found in imaging studies to be capable of trafficking systemically to tumors in mouse models. We therefore examined whether these cells could be used as delivery vehicles to carry oncolytic viruses to the tumor, so increasing the therapeutic benefit of both therapies. We showed that certain strains of vaccinia virus could lie dormant in the CIK cells while they travelled to the tumor. Once deep within the tumor the virus began to replicate and was released from the cell. The CIK cells retained their own ability to target tumor cells despite being infected and the released virus actually worked to attract more of the infected CIK cells into the tumor, so creating a synergy between the two therapies. The combined therapy was found to be more effective at treating different tumor models than single therapies. Immunodeficient mice with human ovarian tumors displayed up to 100% complete responses and immunocompetent mice with breast cancers displayed 75% complete responses when the combination therapy were used. As both these therapies are already in the clinic as single agents we hope to be able to introduce the combined therapy into clinical trials in the near future.
Bibliographical reference:
Steve Thorne Departments of Pediatrics and Bio-X Program, Stanford University School of Medicine, Stanford, CA, USA
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