HUMAN GENE-THERAPY FOR MELANOMA - CT-GUIDED INTERSTITIAL INJECTION

OBJECTIVE. Our intent is to describe the role of CT in the intratumora l injection of Allovectin-7 (Vicar, San Diego, CA), an allogeneic clas s I major histocompatibility complex antigen, HLA-B7, formulated with cationic lipid, in the treatment of metastatic malignant melanoma. MAT ERIALS AND METHODS, Ten patients with metastatic malignant melanoma we re treated with gene therapy in which we used CT-guided intratumoral i njection of plasmid DNA containing the HLA-B7 gene. This therapy was p art of a phase I gene therapy trial in patients with metastatic melano ma. CT guidance was chosen as an accurate way to direct gene delivery in patients with deep, impalpable lesions. Tumor locations included pu lmonary, mediastinal, hepatic, adrenal, and paracaval sites. Patients in the CT protocol underwent baseline CT studies. Examinations were re peated 2, 4, and 8 weeks after gene therapy and thereafter at 3-month intervals. Both injected and noninjected tumors were measured. CT-guid ed injections of 10, 50, or 250 mu g of plasmid DNA were performed wit h 22-gauge spinal needles. Injection Volumes were between 1.0 and 4.0 ml, depending on tumor size. CT-guided core biopsy specimens were obta ined (with 18- or 20-gauge needles) from the selected tumor before the rapy and 2, 4, and 8 weeks after therapy to assess HLA-B7 plasmid DNA and gene expression. Peripheral blood was analyzed for cytotoxic T lym phocytes directed against HLA-B7. RESULTS, CT-guided intratumoral inje ctions were successful in delivering genetic material to all patients with impalpable tumors. Significant responses (as defined by a decreas e of 25% or more in the product of the length and width of the injecte d tumor) were observed in six of the 10 patients. One of these six pat ients who had a solitary lesion remains free of disease 19 months afte r gene therapy. HLA-B7 protein expression was detected in 89% of biops y specimens, and plasmid DNA and messenger RNA were detected in 56% an d 22% of biopsy specimens, respectively. CONCLUSION, CT provides a saf e, accurate, and efficacious way to monitor and assess tumor progressi on and response, and it provides guidance for biopsies and intratumora l injections during gene therapy. Significant responses in injected tu mors of six of the 10 patients in our study suggest that further clini cal trials of this gene therapy are warranted.