The Analysis of Peri-Tumor Necrosis Following the Subcutaneous Implantation of Autologous Tumor Cells Transfected with an Episome Transcribing an Antisense Insulin-Like Growth Factor 1 RNA in a Glioblastoma Multiforme Subject
ADISAK WONGKAJORNSILP, M.D., Ph.D.*, MONGKOL OUYPRASERTKUL, M.D.***, TUMTIP SANGRUCHI, M.D.***, SUKIT HUABPRASERT, Cert. in M.S.T.*, YUEXIN PAN, Ph.D.*****, NANTASAK TISAVIPAT, M.D.**, VORA VUT CHANYAVANICH, M.D.**, SUPATRA SANGRUCHI, M.D.****, KARUNA CHOMSAMUT, B.Sc.**, DONALD D. ANTHONY, M.D.*****
Affiliation : * Department of Pharmacology, **Department of Surgery, ***Department of Pathology, ****Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. *****Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA.
A subject inflicted with glioblastoma multiforme who received partial tumor resection and radiotherapy was recruited for an ex vivo gene therapy protocol using irradiated autologous tumor cells that had been engineered to suppress the expression of insulin-like growth factor I as the tumor vaccine. After subcutaneous injection for 8 weeks, the subject developed peri-tumor necro- sis with mass effect. The authors wondered whether this event could have resulted from the tumor vaccine. The tissue section bordering the necrotic tumor tissue to the viable normal tissue was examined for nature of any infiltrated cells and their activities. Lymphocytes, macrophages, and a small number of neutrophils diffused into the necrotic tumor tissue were found. The infiltrated lymphocytes consisted of both CD4+ and CDS+ T cells. The functional activity of these lympho- cytes was demonstrated by the active production of interferon y and tumor necrosis factor a based on the respective immunofluorescent staining localized to these cells. This finding is compatible with the proposed mechanism underlying the tumor vaccination. However, the contribution of radia- tion treatment to this event cannot be clearly ruled out.
Keywords : Peri-Tumor Necrosis, Insulin-Like Growth Factor 1, Glioblastoma Multiforme, Gene Therapy
