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.
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.
Authors: Nicholas Favalli; Gabriele Bassi; Christian Pellegrino; Jacopo Millul; Roberto De Luca; Samuele Cazzamalli; Su Yang; Anika Trenner; Nour L Mozaffari; Renier Myburgh; Mustafa Moroglu; Stuart J Conway; Alessandro A Sartori; Markus G Manz; Richard A Lerner; Peter K Vogt; Jörg Scheuermann; Dario Neri Journal: Nat Chem Date: 2021-04-08 Impact factor: 24.427
Authors: Luigi Aloj; Laura D'Ambrosio; Michela Aurilio; Anna Morisco; Ferdinando Frigeri; Corradina Caraco'; Francesca Di Gennaro; Gaetana Capobianco; Leonardo Giovannoni; Hans D Menssen; Dario Neri; Antonio Pinto; Secondo Lastoria Journal: Eur J Nucl Med Mol Imaging Date: 2014-01-17 Impact factor: 9.236
Authors: David S Guttery; Rachael A Hancox; Kellie T Mulligan; Simon Hughes; Sinead M Lambe; J Howard Pringle; Rosemary A Walker; J Louise Jones; Jacqueline A Shaw Journal: Breast Cancer Res Date: 2010-08-02 Impact factor: 6.466