title: Immunocytokines: a novel class of potent armed antibodies.
abstract: Several cytokines have been investigated in clinical trials, based on their potent therapeutic activity observed in animal models of cancer and other diseases. However, substantial toxicities are often reported at low doses, thus preventing escalation to therapeutically active regimens. The use of recombinant antibodies or antibody fragments as delivery vehicles promises to enhance greatly the therapeutic index of pro-inflammatory and anti-inflammatory cytokines. This review surveys preclinical and clinical data published in the field of antibody-cytokine fusions (immunocytokines). Molecular determinants (such as molecular format, valence, target antigen), which crucially contribute to immunocytokine performance in vivo, are discussed in the article, as well as recent trends for the combined use of this novel class of biopharmaceuticals with other therapeutic agents.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Zürich, Switzerland.
authors.forename: Nadine
authors.initials: N
authors.lastname: Pasche
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D058990:Molecular Targeted Therapy; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; C528643:F8 monoclonal antibody; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins