High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy

• Published in: Clinical cancer research Vol. 14; no. 24; pp. 7981 - 7986
• Main Authors: Zhang, Yujian, Pastan, Ira
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 15-12-2008
• Subjects: Antigens, Neoplasm - analysis; Extracellular Fluid - immunology; Humans; Immunoconjugates - therapeutic use; Neoplasms - immunology; Neoplasms - therapy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0324

Shedding of cell surface antigens is an important biological process that is used by cells to modulate responses to signals
in the extracellular environment. Because antibody-based therapies of cancer target cell surface antigens, it is important
to understand more about the shedding process and how it affects tumor responses to this type of therapy. Up to now most attention
has been focused on measuring the concentration of shed antigens in the blood and using these to determine the presence of
a tumor and as a measure of response. The recent finding that the concentration of the tumor antigen mesothelin is extremely
high within the interstitial space of tumors, where it can block antibody action, and that the concentration of shed mesothelin
within the tumor is lowered by chemotherapy has important implications for the successful treatment of solid tumors by immunoconjugates
and whole antibodies.