Malignant gliomas are one of the most incurable forms of cancer, attacking the brains of children or adults and causing death, on average, by 1-2 years. We have been employing tumor-selective viruses that will specifically attack these cancers in the brain and 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.
Dr. Bartlett has continued his research on the AAV virus in creating vectors for use in gene therapy. His work in developing these vectors provides promising opportunities for the future of ovarian cancer and other cancer treatment as an alternative method of delivering specific genetic information to cancer cells. Dr. Bartlett has also been working on engineering a resistance to the HIV-1 infection through the use of gene therapy.
He and a team of researchers have developed and studied an anti-HIV lentiviral vector capable of generating cellular resistance to multiple strains of HIV in two different ways. Many animals treated with the vector-modified cells had no detection of the HIV virus in the bloodstream, whereas it was easily detected in the control group not treated with the cells. Dr. Bartlett’s research on vectors is likely to progress the field of gene therapy treatment for both cancer, HIV, and potentially other diseases as well.
Ovarian cancer is one of the most common and frequently life-threatening malignancies affecting women in the U.S. today: about 25,000 new cases will be diagnosed with the disease this year and over 15,000 women will die from it. Delivering therapeutic genes efficiently and precisely, so that they reach only the targeted cancer cells, is crucial to success. My group has developed a means of delivering therapeutic genes to a specific population of cells in laboratory experiments.
By rearranging the genetic structure of AAV, a common human virus, we have created a class of molecular Trojan horse viruses, known as vectors, from the Latin “to carry”. These vectors are aimed at ovarian cancer cells via key sequences in the virus shell that allows it to infect only cells in the body displaying a particular marker that is restricted to cancer cells. We are now testing the Trojan horse system’s ability to cure ovarian cancer in laboratory animals. If these studies are successful, this research will help pave the way for clinical trials in women with ovarian cancer and may lead to a new approach to this deadly disease.