Antigen Shedding May Improve Efficiencies for Delivery of Antibody-Based Anticancer Agents in Solid Tumors

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 13; pp. 3143 - 3152
• Main Authors: PAK, Youngshang, YUJIAN ZHANG, PASTAN, Ira, LEE, Byungkook
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-07-2012
• Subjects: Antibodies - therapeutic use; Antigens - immunology; Antineoplastic agents; Biological and medical sciences; Humans; Immunotherapy; Medical sciences; Models, Theoretical; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - immunology; Neoplasms - therapy; Pharmacology. Drug treatments; Tumors; Antineoplastic agent; Antigen; Performance evaluation; Delivery system; Solid tumor; Antibody; Treatment efficiency; Mesothelin; Malignant tumor; Technique; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-11-3925

Recombinant immunotoxins (RIT) are targeted anticancer agents that are composed of a targeting antibody fragment and a protein toxin fragment. SS1P is a RIT that targets mesothelin on the surface of cancer cells and is being evaluated in patients with mesothelioma. Mesothelin, like many other target antigens, is shed from the cell surface. However, whether antigen shedding positively or negatively affects the delivery of RIT remains unknown. In this study, we used experimental data with SS1P to develop a mathematical model that describes the relationship between tumor volume changes and the dose level of the administered RIT, while accounting for the potential effects of antigen shedding.