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Clin Cancer Res. 2006 May 15;12(10):3200-8.

Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C.

Author information

1
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Z├╝rich, Switzerland.

Abstract

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, approximately 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.

PMID:
16707621
DOI:
10.1158/1078-0432.CCR-05-2804
[Indexed for MEDLINE]
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