Application of interleukin-2-secreting syngeneic/allogeneic fibroblasts in the treatment of primary and metastatic brain tumors.
We found previously that mice injected intracerebrally (i.c.) with a mixture of malignant cells and allogeneic fibroblasts genetically engineered to secrete interleukin-2 (IL-2) survived longer than mice in various control groups. The primary goal of this study was to determine if an established i.c. glioma (Gl261) or breast carcinoma (SB-5b) could be treated by injection of IL-2-secreting allogeneic fibroblasts into the tumor region. As an additional objective, these results were compared with the effectiveness of injecting IL-2-secreting allogeneic fibroblasts prior to the introduction of the tumor cells as a means of preventing the development of an i.c. glioma or breast carcinoma. The results demonstrated that treatment of mice bearing an established i.c. glioma or breast carcinoma with IL-2-secreting allogeneic fibroblasts resulted in a prolonged survival. Furthermore, the results demonstrate a significant delay (P<.005) in the development of glioma in the animals treated with either allogeneic nonsecreting or IL-2-secreting fibroblasts prior to introduction of tumor cells. In addition, 50% of the animals pretreated with IL-2-secreting allogeneic fibroblasts injected subsequently with Gl261 glioma cells did not develop a tumor, whereas all of the animals injected with glioma cells alone and 92% of those treated with nonsecreting fibroblasts eventually died. Evidence also exists that long-term immunity was established in the treated animals because there was a significant prolongation of survival in comparison to naïve controls (P<.01) for those animals without evidence of glioma that previously had been immunized with treatment cells when challenged again with tumor cells. In a parallel experiment, 62% of the animals pretreated with nonsecreting allogeneic fibroblasts and 75% of the animals pretreated with allogeneic IL-2-secreting fibroblasts subsequently injected with SB-5b breast carcinoma cells did not develop tumors. The results indicate that IL-2-secreting allogeneic fibroblasts can be effective in the treatment of an established brain tumor. These data also suggest that i.c. injection of allogeneic IL-2-secreting fibroblasts is effective in prevention of the development of a brain tumor when the fibroblasts are introduced into the same site where the tumor is subsequently injected.
Lichtor
Terry
T
Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research, Chicago, IL 60612, USA. tlichtor@rush.edu
Glick
Roberta P
RP
Tarlock
Katherine
K
Moffett
Shannon
S
Mouw
Elizabeth
E
Cohen
Edward P
EP
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000628:therapy*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005910:Glioma / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007376:Interleukin-2