title: Immunotoxins in cancer therapy: Review and update.
abstract: Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes. This article will also review different generations of immunotoxins with special focus on immunotoxins which are under clinical trials or approved for clinical use. Finally, current deimmunization strategies for development of new less-immunogenic recombinant immunotoxins will be discussed.
  
  
  
  mAbs: Monoclonal antibodies; EF2: elongation factor 2; ITs: Immunotoxins; DT: Diphtheria toxin; PE: Pseudomonas exotoxin; dgA: de-glycosylated A-chain of ricin; rGel: recombinant de-glycosylated form of gelonin; NKC: natural killer cells; HTR: human transferrin receptor; EGF: epidermal growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; DAB389: truncated Diphtheria toxin; B-CCL: B-cell chronic lymphocytic leukemia; RCC: renal cell carcinoma; GVHD: Graft-versus-host disease; EGFR: epidermal growth factor receptor; AML: acute myeloid leukemia; Fab: fragment antigen-binding; dsFv: disulfide-stabilized fragment variable; scFv: single-chain fragment variable; B-ALL: B-lineage Acute Lymphoblastic Leukemia; Fv: fragment variable; HCL: hairy cell leukemia; IL-2R: Interleukin-2 receptor; CR: complete response; CLL: chronic lymphocytic leukemia; ATL: adult T-cell leukemia; DARPins: designed Ankyrin repeat proteins; pmol: picomolar; HAMA: human-anti mouse antibody.
authors.affiliation: a Department of Medical Laboratory Sciences , School of Paramedicine, Kermanshah University of Medical Sciences , Kermanshah , Iran.|b Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|c Student Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Akbari
authors.affiliation: b Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Safar
authors.initials: S
authors.lastname: Farajnia
authors.affiliation: d Biotechnology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Ahdi Khosroshahi
authors.affiliation: a Department of Medical Laboratory Sciences , School of Paramedicine, Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Safari
authors.affiliation: d Biotechnology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Yousefi
authors.affiliation: a Department of Medical Laboratory Sciences , School of Paramedicine, Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Dariushnejad
authors.affiliation: d Biotechnology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Rahbarnia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003888:Desensitization, Immunologic; D004167:Diphtheria Toxin / Q000627:therapeutic use; D053804:Granzymes / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D012260:Ribonucleases / Q000627:therapeutic use; D054789:Ribosome Inactivating Proteins, Type 1 / Q000627:therapeutic use; D012276:Ricin / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D012276:Ricin; D012260:Ribonucleases; D053804:Granzymes
keywords: Cancer targeted therapy; Immunogenicity; Immunotoxin