Formulated Delivery of Enzyme/Prodrug and Cytokine Gene Therapy to Promote Immune Reduction of Treated and Remote Tumors in Mouse Models of Prostate Cancer

Prostate cancer is the second highest cause of cancer death in men in Western society. Early disease is treatable by surgery or radiation, but once late stage disease becomes refractory to hormone removal, patient care is limited to pain management. New treatments are needed. We use gene therapy, al...

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Bibliographic Details
Main Authors: Russell, Pamela J, Khatri, Aparajita, Husaini, Yasmin, Chapman, Jane
Format: Report
Language:English
Subjects:
BACTERIA
CELLS(BIOLOGY)
CYTOKINE GENE THERAPY
CYTOKINES
DISEASES
ENZYMES
GENE THERAPY
GENES
Genetic Engineering and Molecular Biology
HEALTH CARE FACILITIES
HORMONES
IMMUNE REDUCTION
IMMUNITY
Medicine and Medical Research
MOLECULES
MOUSE MODELS
PAIN
PATIENTS
PHOSPHORUS TRANSFERASES
PROSTATE CANCER
PROTEINS
SURGERY
TOXINS AND ANTITOXINS
TRANSFECTION
URACILS
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Summary:Prostate cancer is the second highest cause of cancer death in men in Western society. Early disease is treatable by surgery or radiation, but once late stage disease becomes refractory to hormone removal, patient care is limited to pain management. New treatments are needed. We use gene therapy, alone and in combination with hormones called cytokines that stimulate the immune system. The concept is that delivering a cell-killing agent to an accessible tumor, coupled with help from the immune system can promote tumor reduction both at the treatment site and at remote locations. In this therapy, a gene (a fusion of cytosine deaminase and uracil phosphoribosyltransferase (CD/UPRT)) is delivered to a cancer cell by a virus, or expressed by molecular engineering, so that harmless bacterial proteins are made. When followed by a pro-drug, 5 fluorocytosine (5FC), cancer cells that make CD/UPRT convert SF0 to a toxin that kills the original and neighbouring cells. This system works in slow growing tumors like prostate cancer. Killing the tumor cells attracts immune cells. We are identifying these and then delivering cytokine genes that attract more immune cells into the tumors. We will deliver the cytokine gene alone or with the suicide gene because in other studies, combination therapy works better. The original document contains color images.