Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells Journal Article
| Authors: | Connor, J.; Bannerji, R.; Saito, S.; Heston, W.; Fair, W.; Gilboa, E. |
| Article Title: | Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells |
| Abstract: | This study explored the use of interleukin 2 (IL-2) and interferon γ (IFN-γ) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-γ genes were introduced and expressed in MBT-2 cells. The tumor-forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL2- or IFN-γ-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2-or IFN-γ-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-γ-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the “cured” mice. © 1993, Rockefeller University Press., All rights reserved. |
| Keywords: | cancer survival; controlled study; nonhuman; animal cell; mouse; animal; mice; interleukin 2; animal experiment; animal model; tumor regression; tumor cells, cultured; bladder tumor; immunotherapy; gamma interferon; gene therapy; remission induction; immunomodulation; bladder neoplasms; neoplasm transplantation; tumor cell vaccine; carcinoma, transitional cell; vaccines; interleukin-2; cell secretion; immunization; intradermal drug administration; interferon type ii; human; priority journal; article; support, non-u.s. gov't |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 177 |
| Issue: | 4 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1993-04-01 |
| Start Page: | 1127 |
| End Page: | 1134 |
| Language: | English |
| DOI: | 10.1084/jem.177.4.1127 |
| PUBMED: | 8459207 |
| PROVIDER: | scopus |
| PMCID: | PMC2190983 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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