In vivo characterization of fusion protein comprising of al subunit of shiga toxin and human GM-CSF: assessment of its immunogenicity and toxicity

ABSTRACT

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. In the present study, the recombinant Shiga toxin Al subunit fused to human granulocyte-macrophage colony stimulating factor [Al-GM-CSF], previously produced in E. coll, was further characterized. 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. The lymphocyte proliferation assay, induction of specific IgG response and a mixed [Thl/Th2] response were observed only in BALB/c mice. The mixed response in BALB/c mice [Thl/Th2] could be explained on the basis of the two components of the fusion protein i.e. Al and GM-CSF