Recent Advances at Penn in Ovarian Cancer Therapy
The Coukos laboratory discovered that T cells infiltrate ovarian cancer and predict improved survival. Based on this observation, the Coukos and June laboratories are developing adoptive T cell therapy for ovarian cancer.
T cells may be derived a) from tumors removed surgically, or b) from peripheral blood. T cells removed from tumors following surgery can be manipulated in the lab to select T cells that specifically recognize and kill tumors. T cells with tumor specificity can then be expanded in the lab using technology developed by Dr June. Billions of T cells can be developed within weeks and can then be re-infused to the patient. Alternatively, T cells derived from blood can be engineered in the lab using gene therapy to recognize tumor targets. These T cells with tumor specificity can then be expanded in the lab and re-infused to the patient.
Dr. Coukos’ laboratory is also engineering lymphocytes that recognize tumor vascular targets with the aim of attacking and destroying the tumor vasculature, which is crucial for tumor survival and growth beyond 2 to 3 millimeters. Dr. June’s lab is engineering lymphocytes to redirect them against tumor cell targets. In this approach, lymphocytes are made capable of attacking tumor cells.
Early evidence of the power of immune therapy in ovarian cancer is provided by the results obtained at Penn in a clinical trial of gene-immune therapy using adenovirus delivering interferon-beta. One patient with ovarian cancer metastatic to the chest was treated with this approach. Following a single administration of this vector, we documented dramatic response of the tumor. This response was further strengthened by addition of a drug that shuts off blood supply to the tumor. These data show that immune therapy and combination with biological therapy holds marked promise in ovarian cancer.
The Coukos and June labs have also discovered mechanisms of tumor immune evasion in ovarian cancer and are developing approaches to enhance tumor response to immune therapy. These approaches will be moved to the clinic within the next year.
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