The purpose of this study was to determine the safety, toxicity, and antitumor immune response following S.C. immunizations with a mixture of irradiated, autologous tumor cells and autologous fibroblasts that were genetically modified to express the gene for interleukin 2 (IL-2) in patients with colorectal carcinoma. Ten patients were treated with a fixed dose of tumor cells (10(7)) and escalating doses of fibroblasts secreting IL-2 (per 24 h): 100 units (three patients), 200 units (three patients), 400 units (three patients), and 800 units (one patient). Pre- and posttreatment peripheral blood mononuclear cells were evaluated for evidence of antitumor immune responses. Fatigue and/or flu-like symptoms were experienced by seven patients and delayed-type hypersensitivity-like skin reactions were observed at the sites of the second or subsequent vaccinations in five patients. Low frequencies of tumor cytotoxic T-cell precursors (range, 1/190,000-1/1,320,000 peripheral blood mononuclear cells) were detected prior to therapy in four of seven patients. There was a 5-fold increase following treatment in the frequency of tumor cytotoxic T-cell precursors in two of six evaluable patients. Some patients with colorectal cancer have low frequencies of tumor cytotoxic T-cell precursors that may be increased by this well-tolerated form of IL-2 gene therapy, which warrants continued clinical evaluation.

A patient with glioblastoma multiforme (GBM) who had failed conventional therapy was treated with IL-2 gene therapy. The patient received 10 subcutaneous immunizations with autologous tumor cells and fibroblasts genetically modified to secrete IL-2 by retroviral gene transfer. An antitumor immune response mediated in part by CD8+ cytotoxic T cells was demonstrated with the patient's peripheral blood mononuclear cells. A magnetic resonance imaging (MRI) scan performed 4 weeks after the highest treatment dose revealed marked tumor necrosis. These results support the evaluation of this form of IL-2 gene therapy in additional patients with glioblastoma.

Human Gene TherapyVol. 6, No. 2 News and CommentsInjection of Colon Carcinoma Patients with Autologous Irradiated Tumor Cells and Fibroblasts Genetically Modified to Secrete Interleukin-2 (IL-2): A Phase I Study. San Diego Regional Cancer Center, San Diego, CaliforniaSTUDY CO-CHAIRS Robert E. Sobol, Ivor Royston, CO-INVESTIGATORS Habib Fakhrai, Daniel L. Shawler, Colette Carson, Oliver Dorigo, Ruth Gjerset, Daniel P. Gold, James Koziol, Dan Mercola, Chuck Van Beveren, and Darcy WilsonSTUDY CO-CHAIRS Robert E. SobolSearch for more papers by this author, Ivor RoystonSearch for more papers by this author, CO-INVESTIGATORS Habib FakhraiSearch for more papers by this author, Daniel L. ShawlerSearch for more papers by this author, Colette CarsonSearch for more papers by this author, Oliver DorigoSearch for more papers by this author, Ruth GjersetSearch for more papers by this author, Daniel P. GoldSearch for more papers by this author, James KoziolSearch for more papers by this author, Dan MercolaSearch for more papers by this author, Chuck Van BeverenSearch for more papers by this author, and Darcy WilsonSearch for more papers by this authorPublished Online:19 Mar 2008https://doi.org/10.1089/hum.1995.6.2-195AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byDUAL-TARGETED ANTITUMOR EFFECTS AGAINST BRAINSTEM GLIOMA BY INTRAVENOUS DELIVERY OF TUMOR NECROSIS FACTOR-RELATED, APOPTOSIS-INDUCING, LIGAND-ENGINEERED HUMAN MESENCHYMAL STEM CELLSNeurosurgery, Vol. 65, No. 3Interleukin-2: Evaluation of Routes of Administration and Current Delivery Systems in Cancer TherapyJournal of Pharmaceutical Sciences, Vol. 98, No. 7Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels12 March 2002 | Cancer Gene Therapy, Vol. 9, No. 3Molekulare TherapieCANCER VACCINESHematology/Oncology Clinics of North America, Vol. 15, No. 4Immunological Gene Therapy with ex Vivo Gene-Modified Tumor Cells: A Critique and a Reappraisal Giorgio Parmiani, Monica Rodolfo, and Cecilia Melani6 July 2004 | Human Gene Therapy, Vol. 11, No. 9Gene therapy strategies for colon cancerMolecular Medicine Today, Vol. 6, No. 2Viral-based therapies for liver cancerHPB, Vol. 2, No. 3Cancer gene and immunotherapy: recent developmentsMedical Oncology, Vol. 16, No. 2ENHANCED ANTITUMOR EFFECTS OF BONE MARROW TRANSPLANTATION IN COMBINATION WITH FIBROBLAST-MEDIATED IL-2 AND IL-3 GENE THERAPYTransplantation, Vol. 67, No. 9Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancerPathology & Oncology Research, Vol. 5, No. 1Cancer VaccinesJournal of Clinical Oncology, Vol. 17, No. 3Cytokine Gene Therapy for Human TumorsSurgical Oncology Clinics of North America, Vol. 7, No. 3GENE THERAPY FOR COLON CANCERHematology/Oncology Clinics of North America, Vol. 12, No. 3Augmentation of Hematopoiesis by Fibroblast-Mediated Interleukin-6 Gene Therapy in Mice with Chemotherapy XUETAO CAO, RONG CAI, DIAN WEN JU, QUN TAO, YIZHI YU, and JIANLI WANG27 March 2009 | Journal of Interferon & Cytokine Research, Vol. 18, No. 4ACCELERATED RECOVERY OF IRRADIATION-INDUCED BONE MARROW DEPRESSION BY FIBROBLAST-MEDIATED INTERLEUKIN 6 GENE THERAPY IN COMBINATION WITH BONE MARROW TRANSPLANTATION IN MICE1Transplantation, Vol. 65, No. 3Immunostimulatory cytokines in somatic cells and gene therapy of cancerCytokine & Growth Factor Reviews, Vol. 8, No. 2Tumor Immunotherapy by Vaccination with Cytokine Gene Transfected Cells10 July 2009 | International Reviews of Immunology, Vol. 14, No. 2-3Augmented Antitumor Effects of Killer Cells Induced by Tumor Necrosis Factor Gene-Transduced Autologous Tumor Cells from Gastrointestinal Cancer Patients Yasushi Sato, Yoshikazu Koshita, Michiaki Hirayama, Tomohiko Matuyama, Hiroaki Wakimoto, Hirofumi Hamada, and Yoshiro Niitsu20 March 2008 | Human Gene Therapy, Vol. 7, No. 15 Volume 6Issue 2Feb 1995 InformationCopyright 1995, Mary Ann Liebert, Inc.To cite this article:STUDY CO-CHAIRS Robert E. Sobol, Ivor Royston, CO-INVESTIGATORS Habib Fakhrai, Daniel L. Shawler, Colette Carson, Oliver Dorigo, Ruth Gjerset, Daniel P. Gold, James Koziol, Dan Mercola, Chuck Van Beveren, and Darcy Wilson.Injection of Colon Carcinoma Patients with Autologous Irradiated Tumor Cells and Fibroblasts Genetically Modified to Secrete Interleukin-2 (IL-2): A Phase I Study. San Diego Regional Cancer Center, San Diego, California.Human Gene Therapy.Feb 1995.195-204.http://doi.org/10.1089/hum.1995.6.2-195Published in Volume: 6 Issue 2: March 19, 2008PDF download