Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C
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Date
2006-05
Publication Type
Journal Article
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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, ∼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.
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published
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Journal / series
Volume
12 (10)
Pages / Article No.
3200 - 3208
Publisher
American Association for Cancer Research
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Subject
tumor targeting; human monoclonal antibodies; antobody phage display; tenascin-C; angiogenesis
Organisational unit
03463 - Neri, Dario (ehemalig) / Neri, Dario (former)
Notes
Accepted 8 March 2006, Received 22 December 2005, Revision received 22 February 2006.