AIM： To demonstrate bone marrow stromal cells （BMSCs） can be used as an attractive target for genetic modification in the treatment of malignant diseases. METHODS： Using a hamster model of biliary cancer, we inves...AIM： To demonstrate bone marrow stromal cells （BMSCs） can be used as an attractive target for genetic modification in the treatment of malignant diseases. METHODS： Using a hamster model of biliary cancer, we investigated the therapeutic effects of interleukin-2 （IL-2） gene-modified BHSCs. Syrian golden hamsters were injected via the femoral vein with 5×10^5 cells of the KIGB-5 biliary cancer cell line （n=20）. One week later, the hamsters were injected intraperitoneally with BMSCs containing Ad/hIL-2 and Ad/△E1, unmodified BHSCs, or RPHI only （control） and observed for 12 wk （n=5/each group）. RESULTS： All hamsters treated with BMSCs containing Ad/hIL-2 survived with no evidence of the disease during this period. In contrast, hamsters in the other three groups showed disseminated metastases involving the lungs as eady as 4 wk.CONCLUSION： Ad/IL-2 therapy is effective in the treatment of biliary cancer.展开更多
It has recently been shown that chimeric toxin composed of IL2 fused tp PE40, a mutant form of Pseudomonas Exotoxin A devoid of its native cell recognition and binding domain was cytotoxic to IL-2 receptor bearing cel...It has recently been shown that chimeric toxin composed of IL2 fused tp PE40, a mutant form of Pseudomonas Exotoxin A devoid of its native cell recognition and binding domain was cytotoxic to IL-2 receptor bearing cells. We here amplified the gene IL-2(60), which cedes for the N-terminal 1-60 amino acids of human IL-2 by PCR. After that, we fused it to PE40 and the new chimeric protein IL-2(60)-PE40 was expressed in E. coli. SDS-PAGE revealed that IL-2(60)-PE40 chimeric protein accounts for more than 18% of total cell proteins. As the region IL-2 binds with its receptor was defined in the N-terminal residues 8-54 of IL-2, such fusion proteins will have the same activity with IL-2-PE40. Following primany purification, IL-2 (60)-PE40 was shown to be very toxic to IL-2 receptor-positive cells but non measurable effect on the cells lacking IL-2 receptors. Such a structure has not been reported by now. The fusion protein is useful for suppressing the immune response in cases of rejection of allografts and organ transplants and as therapeutic agents for the treatment of IL-2 receptor related diseases scuh as autoimmune disease, ATL(adult T-cell leukemia), et al.展开更多
基金Supported by The Asan Institute for Life Sciences of South Korea,No.2003-013
文摘AIM： To demonstrate bone marrow stromal cells （BMSCs） can be used as an attractive target for genetic modification in the treatment of malignant diseases. METHODS： Using a hamster model of biliary cancer, we investigated the therapeutic effects of interleukin-2 （IL-2） gene-modified BHSCs. Syrian golden hamsters were injected via the femoral vein with 5×10^5 cells of the KIGB-5 biliary cancer cell line （n=20）. One week later, the hamsters were injected intraperitoneally with BMSCs containing Ad/hIL-2 and Ad/△E1, unmodified BHSCs, or RPHI only （control） and observed for 12 wk （n=5/each group）. RESULTS： All hamsters treated with BMSCs containing Ad/hIL-2 survived with no evidence of the disease during this period. In contrast, hamsters in the other three groups showed disseminated metastases involving the lungs as eady as 4 wk.CONCLUSION： Ad/IL-2 therapy is effective in the treatment of biliary cancer.
文摘It has recently been shown that chimeric toxin composed of IL2 fused tp PE40, a mutant form of Pseudomonas Exotoxin A devoid of its native cell recognition and binding domain was cytotoxic to IL-2 receptor bearing cells. We here amplified the gene IL-2(60), which cedes for the N-terminal 1-60 amino acids of human IL-2 by PCR. After that, we fused it to PE40 and the new chimeric protein IL-2(60)-PE40 was expressed in E. coli. SDS-PAGE revealed that IL-2(60)-PE40 chimeric protein accounts for more than 18% of total cell proteins. As the region IL-2 binds with its receptor was defined in the N-terminal residues 8-54 of IL-2, such fusion proteins will have the same activity with IL-2-PE40. Following primany purification, IL-2 (60)-PE40 was shown to be very toxic to IL-2 receptor-positive cells but non measurable effect on the cells lacking IL-2 receptors. Such a structure has not been reported by now. The fusion protein is useful for suppressing the immune response in cases of rejection of allografts and organ transplants and as therapeutic agents for the treatment of IL-2 receptor related diseases scuh as autoimmune disease, ATL(adult T-cell leukemia), et al.
