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 language | English |
|---|---|
| Pages (from-to) | 2191-2196 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 12 |
| Issue number | 7 I |
| DOIs | |
| Publication status | Published - Apr 1 2006 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody
AU - De Santis, Rita
AU - Albertoni, Claudio
AU - Petronzelli, Fiorella
AU - Campo, Silvia
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
AU - Paganelli, Giovanni
AU - Carminati, Paolo
PY - 2006/4/1
Y1 - 2006/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33646259010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646259010&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-2526
DO - 10.1158/1078-0432.CCR-05-2526
M3 - Article
C2 - 16609034
AN - SCOPUS:33646259010
VL - 12
SP - 2191
EP - 2196
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 7 I
ER -