Low and High Tenascin-Expressing Tumors Are Efficiently Targeted by ST2146 Monoclonal Antibody

Santis, Rita De; Albertoni, Claudio; Petronzelli, Fiorella; Campo, Silvia; D'Alessio, Valeria; Rosi, Antonio; Anastasi, Anna Maria; Lindstedt, Ragnar; Caroni, Nadia; Arseni, Brunilde; Chiodi, P.; Verdoliva, Antonio; Cassani, Giovanni; Chinol, Marco; Paganelli, Giovanni; Carminati, Paolo

doi:10.1158/1078-0432.ccr-05-2526

Cited by 25 publications

(12 citation statements)

References 19 publications

(15 reference statements)

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“…The TNC probe was also detected in liver tissues either due to hepatobiliary clearance or due to the fact that TNC shows low level expression in normal liver sinusoids (Van Eyken et al, 1990). In addition, the ratio of anti-TNC Affimer binders in tumour compared to the spleen, for example, was >6 at 24 hr (Figure 5D); in contrast, anti-TNC antibodies took 2 days to reach a tumour/spleen ratio of 5, although this did improve to 20–30 at day 10 (De Santis et al, 2006). Thus the more rapid clearance rate of alternative binding proteins, such as Affimers, compared to antibodies has the potential to allow more rapid imaging of tumours.…”

Section: Resultsmentioning

confidence: 98%

Affimer proteins are versatile and renewable affinity reagents

Tiede

Bedford

Heseltine

et al. 2017

eLife

160

162

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Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents. We selected 12 diverse molecular targets for Affimer selection to exemplify their use in common molecular and cellular applications including the (a) selection against various target molecules; (b) modulation of protein function in vitro and in vivo; (c) labelling of tumour antigens in mouse models; and (d) use in affinity fluorescence and super-resolution microscopy. This work shows that Affimer proteins, as is the case for other alternative binding scaffolds, represent complementary affinity reagents to antibodies for various molecular and cell biology applications.DOI: http://dx.doi.org/10.7554/eLife.24903.001

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Section: Resultsmentioning

confidence: 98%

Affimer proteins are versatile and renewable affinity reagents

Tiede

Bedford

Heseltine

et al. 2017

eLife

160

162

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“…This therapeutic strategy is particularly appealing in the context of brain malignancies, in consideration of the fact that external beam irradiation of the brain typically should not exceed 30 Gy, and monoclonal antibodies exhibit extremely low uptake in the healthy portion of the brain as a result of the blood-brain barrier function. Vascular tumor-targeting antibodies may efficiently target high-grade astrocytomas in vivo (62,63). The 131 I-labeled antibody L19, which is specific to the alternatively spliced EDB domain of fibronectin, is currently being investigated in combination with whole-brain external beam radiation for the treatment of patients with brain metastases, with encouraging results.…”

Section: Combination Therapymentioning

confidence: 99%

Antibody-Radionuclide Conjugates for Cancer Therapy: Historical Considerations and New Trends

Steiner

Neri²

2011

Clinical Cancer Research

143

129

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When delivered at a sufficient dose and dose rate to a neoplastic mass, radiation can kill tumor cells. Because cancer frequently presents as a disseminated disease, it is imperative to deliver cytotoxic radiation not only to the primary tumor but also to distant metastases, while reducing exposure of healthy organs as much as possible. Monoclonal antibodies and their fragments, labeled with therapeutic radionuclides, have been used for many years in the development of anticancer strategies, with the aim of concentrating radioactivity at the tumor site and sparing normal tissues. This review surveys important milestones in the development and clinical implementation of radioimmunotherapy and critically examines new trends for the antibody-mediated targeted delivery of radionuclides to sites of cancer.

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“…In exploring such a new direction for the development of more effective anticancer chemotherapeutics, it is important to understand the in vivo behavior of the nanocarrier, as the unique distribution governed by the properties of the nanocarrier can change the therapeutic efficacy as well as alter the toxicity profile of the encapsulated drug. In this study, we utilize a mouse xenograft model of human colorectal adenocarcinoma (HT-29) that is known to express tenascin-C [15], [16] and a widely used chemotherapy drug, doxorubicin (DOX), as a model payload to study the biodistribution, antitumor efficacy and toxicity of sulfatide-containing liposomal carrier system.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Antitumor Efficacy and Reduced Systemic Toxicity of Sulfatide-Containing Nanoliposomal Doxorubicin in a Xenograft Model of Colorectal Cancer

Shigdar

et al. 2012

PLoS ONE

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Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX), a sulfatide-containing liposome (SCL) encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX) using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.

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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

Cited by 25 publications

References 19 publications

Affimer proteins are versatile and renewable affinity reagents

Affimer proteins are versatile and renewable affinity reagents

Antibody-Radionuclide Conjugates for Cancer Therapy: Historical Considerations and New Trends

Enhanced Antitumor Efficacy and Reduced Systemic Toxicity of Sulfatide-Containing Nanoliposomal Doxorubicin in a Xenograft Model of Colorectal Cancer

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