Rapid production of interleukin-2-secreting tumor cells by herpes simplex virus-mediated gene transfer: Implications for autologous vaccine production Journal Article
| Authors: | Tung, C.; Federoff, H. J.; Brownlee, M.; Karpoff, H.; Weigel, T.; Brennan, M. F.; Fong, Y. |
| Article Title: | Rapid production of interleukin-2-secreting tumor cells by herpes simplex virus-mediated gene transfer: Implications for autologous vaccine production |
| Abstract: | Production of autologous tumor vaccines would be facilitated by the development of a rapid and efficient method for the transfer of genes into freshly isolated cells. To evaluate the potential of replication defective herpes simplex viral (HSV) amplicon vectors as gene transfer vehicles for tumor vaccine generation, a vector that expresses the human interleukin-2 (IL-2) gene (HSV-IL2) and one that expresses Escherichia coli β-galactosidase (HSVlac) were tested in hepatoma cells of both murine and human origin, gene transfer into murine hepatoma cells (HEPA 1-6) was both rapid and highly efficient: greater than 50% of cells expressed P-Gal when infected at a multiplicity of infection (m.o.i.) of 1 with an exposure period of 20 min. Moreover, gene transfer was as efficient in tumor cells after irradiation with 10,000 rads as in nonirradiated tumor cells. Irradiated HEPA 1-6 cells infected with HSV-IL2 for 20 min secreted IL-2 at a rate of 1,200 ± 160 ng/106 cells per day. C57B1/6J mice immunized with irradiated, HSV-IL-2-transduced tumor cells produced in this way demonstrated specific tumor immunity by in vitro splenocyte tumoricidal activity and by in vivo protection against tumor challenge. Human hepatobiliary tumor specimens harvested at the time of operation, irradiated, and infected with HSV-IL-2 also produced nanogram quantities of IL-2/106 cells per 24 hr. These results indicate that the HSV amplicon vector is a good candidate vehicle for gene transfer in the production of autologous tumor vaccines. By allowing rapid gene transfer to freshly harvested tumor specimens, these vectors bypass the requirement for cell culture and make feasible reinfusion of genetically modified and irradiated autologous cells within hours of tumor harvest. |
| Keywords: | controlled study; human tissue; human cell; nonhuman; carcinoma, hepatocellular; liver neoplasms; animal cell; mouse; animals; mice; animal tissue; interleukin 2; spleen; radiation; animal experiment; animal model; antineoplastic activity; tumor cells, cultured; mice, inbred c57bl; gene transfer; animalia; genetic vectors; cancer vaccines; escherichia coli; gene therapy; beta galactosidase; murinae; simplexvirus; autoantigen; tumor immunity; virus replication; neoplasm transplantation; vaccine production; tumor vaccine; gallbladder neoplasms; herpes simplex virus; herpes; interleukin-2; spleen cell; virus vector; gene transfer techniques; lac operon; cytotoxicity tests, immunologic; infrared radiation; hepatoma cell; hepatobiliary system tumor; humans; human; article |
| Journal Title: | Human Gene Therapy |
| Volume: | 7 |
| Issue: | 18 |
| ISSN: | 1043-0342 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 1996-12-01 |
| Start Page: | 2217 |
| End Page: | 2224 |
| Language: | English |
| PUBMED: | 8953312 |
| PROVIDER: | scopus |
| DOI: | 10.1089/hum.1996.7.18-2217 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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