This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brack, S. S. Articles by Neri, D. Search for Related Content PubMed PubMed Citation Articles by Brack, S. S. Articles by Neri, D.

Tumor-Targeting Properties of Novel Antibodies Specific to the Large Isoform of Tenascin-C

Authors' Affiliations: ¹ Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zürich; and ² Stadtspital Triemli, Chirurgische Klinik ORL, Zürich, Switzerland

Requests for reprints: Dario Neri, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland. Phone: 41-44-633-74-01; Fax: 41-44-633-13-58; E-mail: neri{at}pharma.ethz.ch.

Background: The targeted delivery of bioactive molecules with antibodies specific to tumor-associated antigens represents a promising strategy for improving the efficacy of tumor therapy. The large isoform of tenascin-C, an abundant glycoprotein of the tumor extracellular matrix, is strongly overexpressed in adult tissue undergoing tissue remodeling, including wound healing and neoplasia, and has been implicated in a variety of different cancers while being virtually undetectable in most normal adult tissues.

Experimental Design: We have used antibody phage technology to generate good-quality human recombinant antibodies (F16 and P12) specific to the alternatively spliced domains A1 and D of the large isoform of tenascin-C. The tumor-targeting properties of F16 and P12 were assessed by biodistribution studies in tumor xenografts using the antibodies in small immunoprotein (SIP) format.

Results: SIP(F16) selectively accumulated at the tumor site with 4.5%ID/g at 24 hours in the U87 glioblastoma model but was rapidly cleared from other organs (tumor-to-organ ratios, 10:1). The accumulation of SIP(P12) in the tumor was lower compared with SIP(F16) and persistent levels of radioactivity were observed in the intestine.

Conclusions: These data suggest that the F16 antibody, specific to domain A1 of tenascin-C, is a promising building block for the development of antibody-based pharmaceuticals in view of its excellent tumor-targeting performance and the strong expression of the antigen in a variety of primary and metastatic tumors.

This article has been cited by other articles:

				C. Schliemann, A. Palumbo, K. Zuberbuhler, A. Villa, M. Kaspar, E. Trachsel, W. Klapper, H. D. Menssen, and D. Neri Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2 Blood, March 5, 2009; 113(10): 2275 - 2283. [Abstract] [Full Text] [PDF]

				K. Zuberbuhler, A. Palumbo, C. Bacci, L. Giovannoni, R. Sommavilla, M. Kaspar, E. Trachsel, and D. Neri A general method for the selection of high-level scFv and IgG antibody expression by stably transfected mammalian cells Protein Eng. Des. Sel., March 1, 2009; 22(3): 169 - 174. [Abstract] [Full Text] [PDF]

				J. Marlind, M. Kaspar, E. Trachsel, R. Sommavilla, S. Hindle, C. Bacci, L. Giovannoni, and D. Neri Antibody-Mediated Delivery of Interleukin-2 to the Stroma of Breast Cancer Strongly Enhances the Potency of Chemotherapy Clin. Cancer Res., October 15, 2008; 14(20): 6515 - 6524. [Abstract] [Full Text] [PDF]

				J.-N. Rybak, C. Roesli, M. Kaspar, A. Villa, and D. Neri The Extra-domain A of Fibronectin Is a Vascular Marker of Solid Tumors and Metastases Cancer Res., November 15, 2007; 67(22): 10948 - 10957. [Abstract] [Full Text] [PDF]

				D. Grabulovski, M. Kaspar, and D. Neri A Novel, Non-immunogenic Fyn SH3-derived Binding Protein with Tumor Vascular Targeting Properties J. Biol. Chem., February 2, 2007; 282(5): 3196 - 3204. [Abstract] [Full Text] [PDF]

				V. Castronovo, D. Waltregny, P. Kischel, C. Roesli, G. Elia, J.-N. Rybak, and D. Neri A Chemical Proteomics Approach for the Identification of Accessible Antigens Expressed in Human Kidney Cancer Mol. Cell. Proteomics, November 1, 2006; 5(11): 2083 - 2091. [Abstract] [Full Text] [PDF]

				E. A. Sausville Respecting cancer drug transportability: a basis for successful lead selection. J Natl Cancer Inst, August 16, 2006; 98(16): 1098 - 1099. [Full Text] [PDF]