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Influence of protein properties and protein modification on biodistribution and tumor uptake of anticancer antibodies, antibody derivatives, and non-Ig scaffolds

Warnders, F-J., Lub-de Hooge, M. N., de Vries, E. G. E. & Kosterink, J. G. W., Nov-2018, In : Medicinal research reviews. 38, 6, p. 1837-1873 37 p.

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  • Influence of protein properties and protein modification on biodistribution and tumor uptake of anticancer antibodies, antibody derivatives, and non‐Ig scaffolds

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DOI

Newly developed protein drugs that target tumor-associated antigens are often modified in order to increase their therapeutic effect, tumor exposure, and safety profile. During the development of protein drugs, molecular imaging is increasingly used to provide additional information on their in vivo behavior. As a result, there are increasing numbers of studies that demonstrate the effect of protein modification on whole body distribution and tumor uptake of protein drugs. However, much still remains unclear about how to interpret obtained biodistribution data correctly. Consequently, there is a need for more insight in the correct way of interpreting preclinical and clinical imaging data. Summarizing the knowledge gained to date may facilitate this interpretation. This review therefore provides an overview of specific protein properties and modifications that can affect biodistribution and tumor uptake of anticancer antibodies, antibody fragments, and nonimmunoglobulin scaffolds. Protein properties that are discussed in this review are molecular size, target interaction, FcRn binding, and charge. Protein modifications that are discussed are radiolabeling, fluorescent labeling drug conjugation, glycosylation, humanization, albumin binding, and polyethylene glycolation.

Original languageEnglish
Pages (from-to)1837-1873
Number of pages37
JournalMedicinal research reviews
Volume38
Issue number6
Publication statusPublished - Nov-2018

    Keywords

  • biodistribution, drug, modification, molecular imaging, protein, POSITRON-EMISSION-TOMOGRAPHY, PLASMA HALF-LIFE, HER2/NEU-OVEREXPRESSING METASTATIC BREAST, NEAR-INFRARED PHOTOIMMUNOTHERAPY, DEPENDENT CELLULAR CYTOTOXICITY, HUMANIZED MONOCLONAL-ANTIBODY, ANTI-HER2 AFFIBODY MOLECULES, ACUTE LYMPHOBLASTIC-LEUKEMIA, PROSTATE-CANCER XENOGRAFTS, MEDIATED DRUG DISPOSITION

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