Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody.

Abstract

ST2146biot is a biotinylated anti-tenascin monoclonal antibody (mAb) to be used for Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) of solid tumors. In vivo biodistribution studies of (125)I-labeled ST2146biot were done in nude mice transplanted with human HT-29 colon carcinoma and/or human U-118MG glioblastoma cells characterized for low and high tenascin expression, respectively. In vitro results show that ST2146 retains immunoreactivity upon biotinylation, in contrast to other anti-tenascin mAbs. In vivo biodistribution of ST2146 shows specific tumor accumulation up to 10 days after the i.v. injection, with no relevant differences between biotinylated and nonbiotinylated ST2146. A dose of 4 microg/mouse saturates the low tenascin-expressing human colon carcinoma HT-29, whereas the high tenascin-expressing human glioblastoma U-118MG seems to be saturated at a ST2146biot dose between 320 and 640 microg/mouse. The percentage of injected dose per gram of tumor ranges from 10% to 30%, corresponding to an amount of ST2146biot/g of tumor of approximately 400 ng/g and >200 microg/g for HT-29 and U-118MG, respectively. Tumor to normal organs uptake ratios are between 15 and 60, confirming high tumor selectivity of ST2146biot despite its cross-reactivity with the tenascin expressed at low level in the normal mouse organs. The ST2146biot localization data are substantially confirmed even when both low and high tenascin-expressing tumors are implanted in the same animal. To our knowledge, the absolute amount of ST2146biot, specifically localized in xenotransplanted human tumors, is the highest thus far described and supports the clinical use of this mAb in PAGRIT(R).

• Authors: Rita De Santis, Claudio Albertoni, Fiorella Petronzelli, Silvia Campo, Valeria D'Alessio, Antonio Rosi, Anna Maria Anastasi, Ragnar Lindstedt, Nadia Caroni, Brunilde Arseni, Pierino Chiodi, Antonio Verdoliva, Giovanni Cassani, Marco Chinol, Giovanni Paganelli, Paolo Carminati
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 7 Pt 1 Pg. 2191-6 (Apr 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16609034 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• ST2146biot
• Tenascin

Topics

• Adenocarcinoma (immunology, metabolism, pathology)
• Animals
• Antibodies, Monoclonal (chemistry, pharmacokinetics)
• Antibody Specificity
• Biotinylation
• Breast Neoplasms (immunology, metabolism, pathology)
• Cell Line, Tumor
• Colonic Neoplasms (immunology, metabolism, pathology)
• Disease Models, Animal
• Drug Screening Assays, Antitumor
• Glioblastoma (immunology, metabolism, pathology)
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Radioimmunotherapy (methods)
• Structure-Activity Relationship
• Tenascin (biosynthesis, immunology)
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays