Augmented antitumor activity of a secondary lymphoid-tissue chemokine (SLC)-interleukin (IL) 2 fusion protein in mouse

✍ Scribed by Koichiro Nakahara; Tsuneaki Sakata

• Book ID: 102343701
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 336 KB
• Volume: 5
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.369

✦ Synopsis

Abstract

Background

To enhance the antitumor efficacy of IL2 gene therapy, combinations of several other genes, such as p53, a tumor suppressor gene, or lymphotactin, a C‐chemokine, and the IL2 gene are attempted, and synergistic effects are observed. We report here on the enhanced antitumor activity of a fusion protein (mSLC‐IL2) comprised of a newly identified member of the CC‐chemokine family, mouse SLC (mSLC), and mouse IL2 (mIL2).

Methods

We constructed mSLC‐IL2 by connecting the N‐terminus of mIL‐2 to the C‐terminus of mSLC using a two‐amino‐acid linker. The resultant fusion protein retained both mIL2 activity, as measured in a standard proliferation assay using a mouse IL‐2 dependent cell line, and chemokine activity, as measured in a chemotaxis assay using a preB cell line expressing mSLC‐specific receptor, CCR7. The gene encoding mSLC‐IL2 was retrovirally transduced into fibroblast CL.7 cells, derived from Balb/c mice.

Results

Intradermal transplantation of fibroblasts expressing mSLC‐IL2 into syngenic mice induced a dense accumulation of CD4^+^ and CD8^+^ cells at the sites of transplantation. Moreover, when CT‐26 cells, derived from colon adenocarcinoma cells, were co‐transplanted with mSLC‐IL2‐transduced fibroblasts, the CT‐26 cell exhibited significantly lower tumorigenicity than CT‐26 cells co‐transplanted with mIL2‐transduced fibroblasts.

Conclusions

These findings, obtained from both in vitro and in vivo data, suggest that the gene encoding mSLC‐IL2 may be a good candidate for inclusion as part of an anticancer gene therapy protocol. Copyright © 2003 John Wiley & Sons, Ltd.