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

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). 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. 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. 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.

Nakahara K ，Sakata T 《JOURNAL OF GENE MEDICINE》

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT.

Hisada M ，Yoshimoto T ，Kamiya S ，Magami Y ，Miyaji H ，Yoneto T ，Tamada K ，Aoki T ，Koyanagi Y ，Mizuguchi J ... -  《CANCER GENE THERAPY》

Herpes simplex virus (HSV) amplicon-mediated codelivery of secondary lymphoid tissue chemokine and CD40L results in augmented antitumor activity.

Tolba KA ，Bowers WJ ，Muller J ，Housekneckt V ，Giuliano RE ，Federoff HJ ，Rosenblatt JD ... -  《CANCER RESEARCH》

Local delivery of recombinant vaccinia virus expressing secondary lymphoid chemokine (SLC) results in a CD4 T-cell dependent antitumor response.

Flanagan K ，Glover RT ，Hörig H ，Yang W ，Kaufman HL ... -  《VACCINE》

Soluble expression of recombinant human secondary lymphoid chemokine (SLC) in E. coli and research on its in vitro and in vivo bioactivity.

Chun L ，Yin CC ，Song JZ ，Liu MX ，Piao JH ，Lin Q ，Wang XB ，Huang HL ... -  《-》