title: The translational potential for target validation and therapy using intracellular antibodies in oncology.
abstract: Antibody-based molecules can be delivered into cells either by intracellular expression or through cellular uptake. We describe technologies for identification and expression of intracellular antibodies for target validation, intracellular immunization and tumor therapy, such as intracellular antibody capture technology, suicide or silencing technology, antigen-antibody interaction dependent apoptosis and their application for inhibition of oncogenic intracellular proteins and induction of apoptosis. These strategies have to be viewed in the context that inhibition of protein-protein interactions by small molecules is often limited due to their large interaction surface. We summarize antibodies with the ability to penetrate cells and strategies to induce uptake of antibodies after modification with protein transduction domains. Interference in oncogenic pathways is described for moieties based on antibody 3E10, which translocates into the nucleus after extracellular administration. Finally, we discuss examples of tumor immunotherapy and vaccination against intracellular antigens, and possible interactions mediating their mode of action.
authors: Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Im Nonnenwald 2, D-82372 Penzberg, Germany. ulrich.weidle@roche.com.
authors: Ulrich H
authors: UH
authors: Weidle
authors: Daniela
authors: D
authors: Maisel
authors: Ulrich
authors: U
authors: Brinkmann
authors: Georg
authors: G
authors: Tiefenthaler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm
keywords: Autoimmune disease-related antibodies; cancer immunotherapy against intracellular targets; inhibition of oncogenic pathways; intracellular immunization; mechanisms of antibody uptake; protein knock-down; protein transduction domain; review; target validation