Selection strategies for anticancer antibody discovery: searching off the beaten path

David Sánchez-Martín; Morten Dræby Sørensen; Simon Lykkemark; Laura Sanz; Peter Kristensen; Erkki Ruoslahti; Luis Álvarez-Vallina

doi:10.1016/j.tibtech.2015.02.008

Selection strategies for anticancer antibody discovery: searching off the beaten path

Trends Biotechnol. 2015 May;33(5):292-301. doi: 10.1016/j.tibtech.2015.02.008. Epub 2015 Mar 26.

Authors

David Sánchez-Martín¹, Morten Dræby Sørensen², Simon Lykkemark³, Laura Sanz⁴, Peter Kristensen⁵, Erkki Ruoslahti⁶, Luis Álvarez-Vallina⁷

Affiliations

¹ Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
² Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Department of Molecular Biology and Genetics, Aarhus University, 8000C Aarhus, Denmark.
³ Department of Clinical Medicine, Aarhus University, 8000C Aarhus, Denmark; Sino-Danish Center, Aarhus University, 8000C Aarhus, Denmark.
⁴ Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Madrid, Majadahonda, 28222 Spain.
⁵ Department of Engineering, Aarhus University, 8000C Aarhus, Denmark.
⁶ 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.
⁷ 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.

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.

Keywords: advanced phage selections; phage display; therapeutic antibodies; tumor-associated antigens.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / therapeutic use
Antibodies, Neoplasm / chemistry*
Antibodies, Neoplasm / therapeutic use
Antigens, Neoplasm / chemistry
Antineoplastic Agents / chemistry*
Antineoplastic Agents / therapeutic use
Cell Surface Display Techniques
Drug Discovery
Humans
Medical Oncology / trends*
Neoplasms / immunology
Neoplasms / therapy*
Tumor Microenvironment

Substances

Antibodies, Monoclonal
Antibodies, Neoplasm
Antigens, Neoplasm
Antineoplastic Agents

Grants and funding

R01 CA188883/CA/NCI NIH HHS/United States