title: In vivo characterization of fusion protein comprising of A1 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 A1 subunit fused to human granulocyte-macrophage colony stimulating factor (A1-GM-CSF), previously produced in E. coli, 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 (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.affiliation: Molecular Biology Unit, Pasteur Institute of Iran, Pasteur Ave. Tehran 13164, Iran.
authors.forename: Mana
authors.initials: M
authors.lastname: Oloomi
authors.affiliation: Molecular Biology Unit, Pasteur Institute of Iran, Pasteur Ave. Tehran 13164, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Bouzari
authors.affiliation: Molecular Biology Unit, Pasteur Institute of Iran, Pasteur Ave. Tehran 13164, Iran.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Shariati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D000922:Immunotoxins / Q000276:immunology* / Q000633:toxicity*; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D020014:K562 Cells; D007928:Lethal Dose 50; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D022621:Shiga Toxin / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; C493898:Shiga toxin subunit A; D015847:Interleukin-4; D022621:Shiga Toxin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor