Allovectin-7 is a gene therapy product containing the gene for the HLA-B7 protein. The HLA-B7 protein causes the cells which contain it to be recognized as a foreign invader by the immune system. The HLA-B7 gene is contained within a small circular piece of bacterial DNA called a plasmid. These plasmids will be mixed with fat bodies, called lipids, and inserted into the tumor by needle injection. Once introduced into the tumor, the cells containing the plasmid DNA produce proteins which, based on animal studies, are thought to stimulate tumor tissue rejection. This research study will be conducted at multiple sites across the country and will enroll approximately 70 subjects with melanoma. The LSUMC site for this study will enroll approximately 12 subjects. This treatment requires injection of the gene substance directly into the subject's tumor(s). These gene injections are thought to induce an immune response to the cancer. The efficacy of Allovectin-7 gene transfer was evaluated in humans in a Phase I/II trial (VCL-1005-101) in patients with metastatic melanoma, renal cell carcinoma, or colorectal adenocarcinoma. Patients received a single dose of 10mg, or 50mg, or 250mg, or multiple doses of 2 x 10mg, or 3 x 10mg of Allovectin-7. Gene transfer was evaluated by PCR, flow cytometric and immunohistochemical analyses of injected tumor biopsies. Immunological responses were evaluated by serology, cytotoxicity assays, and immunohistochemistry of T lymphocyte subset infiltration in tumor biopsies. Gene transfer was confirmed in 32 of 43 patients (74%). HLA-B7 expression was confirmed in 25 out of 43 patients (58%). T-cell infiltrates were detected in 22 of 23 tumor biopsy samples evaluated, and 22 showed elevated CD8 counts. Overall, 39 of the 43 patients (91%) demonstrated either gene transfer of HLA-B7 expression. The lack of detection of gene transfer in the four other patients may not be due to sampling bias. Available human data indicates that VCL-1005 plasmid DNA can be expressed by cells containing VCL-1005 plasmid DNA. When transfection occurs, the HLA-B7 protein expressed becomes incorporated into the MCH on the exterior of the cell membrane. The recipient's immune system recognizes the HLA-B7 antigen as non-self and initiates an immune response against the transfected cells. With direct intratumoral injections of HLA-B7, the tumor cells are transfected, an immune response is elicited, and the tumor cells are destroyed.
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