2007 Clinical Investigator

Antonio E. Chiocca, MD, PhD

Brigham and Women’s Hospital, Harvard Medical School
Chairman, Department of Neurological Surgery

Research Focus: Tumor specific replicating Viruses and Bacterium
Cancer Type: Gene Therapy for Brain Cancer

Dr. Chiocca has continued his work with using viruses as a mechanism to treat brain cancers. Dr. Chiocca has genetically reengineered certain viruses to target tumors in the brain but that leave healthy tissue alone. Animal trails have proven successful and, if successful in humans as well, this treatment could offer a novel, non-invasive approach to cancer therapy. Recently, though, he identified a potential set back to the use of this treatment. Dr. Chiocca found that natural killer cells (NK cells), a type of white blood cell that targets viruses and sometimes tumors within the body, are attacking the virus-infected cells making the treatment much less effective. Dr. Chiocca has identified the specific receptors that allow the NK cells to impede the virotherapy and is currently researching ways to prevent this from happening so that the treatment can work to its full potential and be the most effective it can be against the tumors.

Malignant gliomas are one of the most incurable forms of cancer, attacking the brain of children or adults and causing death, on the average, by 1-2 years. We have been employing tumor-selective viruses that will specifically attack these cancers in the brain and also will sensitize these cancers to the effect of chemotherapy by transferring the genes that activate such chemotherapy drugs. The virus that we have tested in mice with brain tumors is named MGH2 and we now plan to perform preclinical toxicology studies requested by the FDA before proceeding to a human phase I clinical trial. A clinical trial in humans will involve injecting the brain tumor with MGH2 in combination with the two chemotherapy agents, cyclophosphamide and irinotecan, that are converted by the MGH2-transferred genes into the active anticancer agents. This multimodal viro- and gene-based therapy would thus provide the opportunity of attacking multiple vulnerabilities within the malignant brain tumor.

At the time of the Award: Ohio State University Research Foundation, Columbus, Ohio
Chairman, Department of Neurological Surgery

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