BACKGROUND: Most cancer cells become resistant to anti-cancer agents. In the last few years, a new approach for targeted therapy of human cancer has been developed using immunotoxins which comprise both the cell targeting and the cell killing moieties. METHODS: In the present study, the recombinant Shiga toxin A1 subunit fused to human granulocyte-macrophage colony stimulating factor (A1-GM-CSF), previously produced in E. coli, was further characterized. RESULTS: The recombinant protein could cause 50% cytotoxicity and induced apoptosis in cells bearing GM-CSF receptors. The non-specific toxicity of the fusion protein was assessed in C57BL/6 and BALB/c mice. No mortality was observed in either group of mice, with different concentration of fusion protein. CONCLUSION: The lymphocyte proliferation assay, induction of specific IgG response and a mixed (Th1/Th2) response were observed only in BALB/c mice. The mixed response in BALB/c mice (Th1/Th2) could be explained on the basis of the two components of the fusion protein i.e. A1 and GM-CSF.
BACKGROUND: Most cancer cells become resistant to anti-cancer agents. In the last few years, a new approach for targeted therapy of humancancer has been developed using immunotoxins which comprise both the cell targeting and the cell killing moieties. METHODS: In the present study, the recombinant Shiga toxin A1 subunit fused to human granulocyte-macrophage colony stimulating factor (A1-GM-CSF), previously produced in E. coli, was further characterized. RESULTS: The recombinant protein could cause 50% cytotoxicity and induced apoptosis in cells bearing GM-CSF receptors. The non-specific toxicity of the fusion protein was assessed in C57BL/6 and BALB/c mice. No mortality was observed in either group of mice, with different concentration of fusion protein. CONCLUSION: The lymphocyte proliferation assay, induction of specific IgG response and a mixed (Th1/Th2) response were observed only in BALB/c mice. The mixed response in BALB/c mice (Th1/Th2) could be explained on the basis of the two components of the fusion protein i.e. A1 and GM-CSF.
Authors: A E Frankel; J Ramage; A Latimer; T Feely; S Delatte; P Hall; E Tagge; R Kreitman; M Willingham Journal: Protein Expr Purif Date: 1999-06 Impact factor: 1.650
Authors: C E Hotchkiss; P D Hall; J M Cline; M C Willingham; R J Kreitman; J Gardin; A Latimer; J Ramage; T Feely; S DeLatte; E P Tagge; A E Frankel Journal: Toxicol Appl Pharmacol Date: 1999-07-15 Impact factor: 4.219
Authors: Marlena M Westcott; Ralph J Abi-Habib; Kimberley A Cohen; Mark C Willingham; Shihui Liu; Thomas H Bugge; Stephen H Leppla; Arthur E Frankel Journal: Mol Cancer Ther Date: 2004-12 Impact factor: 6.261