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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 125I-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 μg/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 μg/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 ∼ 400 ng/g and >200 μg/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.

Original languageEnglish
Pages (from-to)2191-2196
Number of pages6
JournalClinical Cancer Research
Volume12
Issue number7 I
DOIs
Publication statusPublished - Apr 1 2006

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Tenascin
Monoclonal Antibodies
Neoplasms
Radioimmunotherapy
Glioblastoma
Colon
Biotinylation
Carcinoma
Antibodies
ST2146biot
Nude Mice
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

De Santis, R., Albertoni, C., Petronzelli, F., Campo, S., D'Alessio, V., Rosi, A., ... Carminati, P. (2006). Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody. Clinical Cancer Research, 12(7 I), 2191-2196. https://doi.org/10.1158/1078-0432.CCR-05-2526

Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody. / De Santis, Rita; Albertoni, Claudio; Petronzelli, Fiorella; Campo, Silvia; D'Alessio, Valeria; Rosi, Antonio; Anastasi, Anna Maria; Lindstedt, Ragnar; Caroni, Nadia; Arseni, Brunilde; Chiodi, Pierino; Verdoliva, Antonio; Cassani, Giovanni; Chinol, Marco; Paganelli, Giovanni; Carminati, Paolo.

In: Clinical Cancer Research, Vol. 12, No. 7 I, 01.04.2006, p. 2191-2196.

Research output: Contribution to journalArticle

De Santis, R, Albertoni, C, Petronzelli, F, Campo, S, D'Alessio, V, Rosi, A, Anastasi, AM, Lindstedt, R, Caroni, N, Arseni, B, Chiodi, P, Verdoliva, A, Cassani, G, Chinol, M, Paganelli, G & Carminati, P 2006, 'Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody', Clinical Cancer Research, vol. 12, no. 7 I, pp. 2191-2196. https://doi.org/10.1158/1078-0432.CCR-05-2526
De Santis R, Albertoni C, Petronzelli F, Campo S, D'Alessio V, Rosi A et al. Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody. Clinical Cancer Research. 2006 Apr 1;12(7 I):2191-2196. https://doi.org/10.1158/1078-0432.CCR-05-2526
De Santis, Rita ; Albertoni, Claudio ; Petronzelli, Fiorella ; Campo, Silvia ; D'Alessio, Valeria ; Rosi, Antonio ; Anastasi, Anna Maria ; Lindstedt, Ragnar ; Caroni, Nadia ; Arseni, Brunilde ; Chiodi, Pierino ; Verdoliva, Antonio ; Cassani, Giovanni ; Chinol, Marco ; Paganelli, Giovanni ; Carminati, Paolo. / Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 7 I. pp. 2191-2196.
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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 125I-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 μg/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 μg/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 ∼ 400 ng/g and >200 μg/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.",
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AU - D'Alessio, Valeria

AU - Rosi, Antonio

AU - Anastasi, Anna Maria

AU - Lindstedt, Ragnar

AU - Caroni, Nadia

AU - Arseni, Brunilde

AU - Chiodi, Pierino

AU - Verdoliva, Antonio

AU - Cassani, Giovanni

AU - Chinol, Marco

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AU - Carminati, Paolo

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