Cytokine Gene Therapy with Interleukin-2-Transduced Fibroblasts: Effects of IL-2 Dose on Anti-Tumor Immunity
| Autor: | James A. Koziol, Robert E. Sobol, Daniel L. Shawler, Ruth A. Gjerset, Habib Fakhrai, Robert K. Naviaux, Ivor Royston |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Cytotoxicity
Immunologic Interleukin 2 Colorectal cancer T-Lymphocytes Genetic enhancement Genetic Vectors Gene Expression Mice Nude Adenocarcinoma Cell Line Mice Immune system Immunity Genetics Animals Humans Medicine Cytotoxicity Molecular Biology Immunity Cellular Mice Inbred BALB C business.industry Gene Transfer Techniques Genetic Therapy Fibroblasts medicine.disease Retroviridae Immunization Cell culture Immunology Cancer research Interleukin-2 Molecular Medicine Colorectal Neoplasms business Neoplasm Transplantation medicine.drug |
| Zdroj: | Human Gene Therapy. 6:591-601 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.1995.6.5-591 |
| Popis: | We evaluated the effects of different doses of interleukin-2 (IL-2)-transduced fibroblasts in the treatment of colorectal carcinoma in the CT-26 murine tumor model. Immunization with a mixture of irradiated tumor cells and IL-2-transduced fibroblasts (100 units of IL-2/24 hr) induced significantly greater protection against a live tumor challenge compared to irradiated tumor cells alone (22/35, 65% vs. 10/30, 33%, p < 0.02). Protective effects were observed with doses of IL-2-transduced fibroblasts secreting from 5 to 100 units of IL-2/24 hr. Parallel experiments in nude mice produced no protection, indicating that the effects of immunization were mediated by a T-cell-dependent mechanism. In animals with established tumors, complete tumor remissions were observed following immunization with a mixture of irradiated tumor cells and IL-2-transduced fibroblasts secreting 100 units of IL-2/24 hr, but not after immunization with irradiated tumor cells alone (7/16 vs. 0/11 complete remissions, p < 0.02). Fibroblasts secreting higher doses of IL-2 were ineffective in generating systemic immunity, but were required to prevent tumor implantation. A statistically significant difference in the prevention of tumor implantation was observed between groups inoculated with a mixture of live tumor cells and IL-2-transduced fibroblasts (1,750 units of IL-2/24 hr) compared to control fibroblasts (6/8 vs. 0/12, p < 0.001). Similar results were observed in nude mice, suggesting that the implantation rejection response is mediated in part by cells other than thymus-derived T cells. Our data support the utility of IL-2-transduced fibroblasts and indicate that the level of IL-2 expression is an important variable in activating different effector components of antitumor immune responses in IL-2 gene therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|