title: Selection strategies for anticancer antibody discovery: searching off the beaten path.
abstract: Antibody-based drugs represent one of the most successful and promising therapeutic approaches in oncology. Large combinatorial phage antibody libraries are available for the identification of therapeutic antibodies and various technologies exist for their further conversion into multivalent and multispecific formats optimized for the desired pharmacokinetics and the pathological context. However, there is no technology for antigen profiling of intact tumors to identify tumor markers targetable with antibodies. Such constraints have led to a relative paucity of tumor-associated antigens for antibody targeting in oncology. Here we review novel approaches aimed at the identification of antibody-targetable, accessible antigens in intact tumors. We hope that such advanced selection approaches will be useful in the development of next-generation antibody therapies for cancer.
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sánchez-Martín
authors.affiliation: Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Department of Molecular Biology and Genetics, Aarhus University, 8000C Aarhus, Denmark.
authors.forename: Morten Dræby
authors.initials: MD
authors.lastname: Sørensen
authors.affiliation: Department of Clinical Medicine, Aarhus University, 8000C Aarhus, Denmark; Sino-Danish Center, Aarhus University, 8000C Aarhus, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Lykkemark
authors.affiliation: Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Madrid, Majadahonda, 28222 Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanz
authors.affiliation: Department of Engineering, Aarhus University, 8000C Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Kristensen
authors.affiliation: Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA; Center for Nanomedicine, University of California Santa Barbara, CA 93106, USA; Department of Cell, Molecular, and Developmental Biology, University of California Santa Barbara, CA 93106, USA.
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
authors.affiliation: Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Madrid, Majadahonda, 28222 Spain; Department of Engineering, Aarhus University, 8000C Aarhus, Denmark. Electronic address: lav@eng.au.dk.
authors.forename: Luis
authors.initials: L
authors.lastname: Álvarez-Vallina
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000737:chemistry* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D061505:Cell Surface Display Techniques; D055808:Drug Discovery; D006801:Humans; D008495:Medical Oncology / Q000639:trends*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents
keywords: advanced phage selections; phage display; therapeutic antibodies; tumor-associated antigens
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