Effects of interleukin-2 transduction on the human hepatoma cell lines using retroviral vector

Joo Hang Kim, Soo Jung Gong, Nae Chun Yoo, Heuiran Lee, Dong Hwan Shin, Hyo Dong Uhm, Sook Jung Jeong, Jae Yong Cho, Sun Young Rha, Yeon Soo Kim, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim

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Abstract

Gene therapy, using cytokine gene transduction, aims to increase the antigenicity of tumor cells, and to activate the immune effector cells, and thereby inducing tumor regression. With regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity we compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus. EL-2 secretion was 186 pg/ 106 cells/24 h in SK-Hepl cell line and 147 pg/106 cells/ 24 h in Hep-SB cell line with N2A/IL-2 retroviral vector and was 55,000 pg/106 cells/24 h in Hep-3B cell line with LNC/ IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8-254% in IL-2 transduced hepatoma cell lines (Hep-3B/LNC/IL-2, Hep-G2/LNC/IL-2) compared to those of the parent cell lines. The tumor was formed in 1 of 3 BALB/c mice and all 3 nude mice with the injection of 1×107 cells. Simultaneous injection of 1×107 cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5×105 cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. After injection of 1×107 cells into five other nude mice, the tumor of the IL-2 transduced hepatoma cells (Hep-3B/LNC/IL-2) gradually disappeared, however, the tumor of the parent hepatoma cell line initially decreased and then gradually regrew 20 days later. In conclusion, IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes. IL-2 secretion by LNC/IL-2 retrovirus from the hepatoma cell lines was more prominent compared with that by N2A/IL-2 retrovirus. IL-2 transduction into the hepatoma cells resulted in increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, which leads the regression of the tumors. However, the higher the tumor burden, the less efficient tumor regression by IL-2 transduction into the hepatoma cell line in nude mice was observed.

Original languageEnglish
Pages (from-to)49-54
Number of pages6
JournalOncology reports
Volume6
Issue number1
Publication statusPublished - 1999 Dec 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kim, J. H., Gong, S. J., Yoo, N. C., Lee, H., Shin, D. H., Uhm, H. D., Jeong, S. J., Cho, J. Y., Rha, S. Y., Kim, Y. S., Chung, H. C., Roh, J. K., Min, J. S., & Kim, B. S. (1999). Effects of interleukin-2 transduction on the human hepatoma cell lines using retroviral vector. Oncology reports, 6(1), 49-54.