AvidinOX™ for Highly Efficient Tissue-Pretargeted Radionuclide Therapy

Santis, Rita De; Leoni, Barbara; Rosi, Antonio; Albertoni, Claudio; Forni, Guido; Cojoca, Rodica; Iezzi, Manuela; Musiani, Piero; Paganelli, Giovanni; Chinol, Marco; Carminati, Paolo

doi:10.1089/cbr.2009.0738

Cited by 20 publications

(22 citation statements)

References 28 publications

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“…There is a need to develop local treatments for cancer lesions that are derived from or reside within tissues/organs that are very different in terms of stromal composition, vascularization, density and other features. AvidinOX has been previously shown to form Schiff's bases with proteins in a variety of tissues and in several animal species (7)(8)(9)(10)(11)(12)(13). Long tissue residence of AvidinOX is also currently being confirmed in human patients with liver metastases and other inoperable tumor lesions as indicated by selective and consistent uptake of intravenous 177 Lu-ST2210 administered 1 and up to 15 days after intra-tumor AvidinOX (ClinicalTrials.gov NCT02053324 and NCT03188328, data not shown).…”

Section: Discussionmentioning

confidence: 96%

“…We recently described a novel method that allows suboptimal doses of biotinylated agents to become effective therapies in models of HNC. The treatment is based on the intra-tumor injection of AvidinOX, an oxidized avidin derivative that exhibits the distinctive property of forming Schiff's bases with tissue proteins (7)(8)(9)(10)(11), followed by systemically administered radioactive biotin (12) or biotinylated cetuximab (bCet) (13). In the present study, we show that the injection of AvidinOX into FaDu pharynx squamous cell carcinoma cells xenografted in the mouse tongue increases the anti-tumor activity of a suboptimal bCet dose administered intraperitoneally after 24 h. The data also indicate that the treatment can be repeated at least twice, 1 week apart, and that the therapeutic efficacy could be further improved by including a low dose of cisplatin in the protocol.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic efficacy of intra‑tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer

Vesci

Carollo²,

Rosi

et al. 2019

Oncol Lett

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In a previous study, the efficacy of low intraperitoneal doses of biotinylated cetuximab (bCet) in mice with subcutaneous tumor xenografts of human head and neck cancer (HNC) treated intra-tumors with AvidinOX was reported. Taking into account that the current standard treatment for HNC is the combination of cetuximab and cisplatin, the present study investigated the activity of AvidinOX-targeted bCet with and without cisplatin in an orthotopic model. The results confirmed that administration of intra-tumor AvidinOX makes an otherwise inactive dose of bCet effective in reducing tumor growth, and the addition of a low dose of cisplatin further improved tumor growth inhibition. Supporting the in vivo data, immunohistochemical staining of tumor masses from mice treated with AvidinOX, bCet and cisplatin exhibited the highest tumor cell damage and the lowest angiogenic activity among all treatment groups, measured as the number of γ-H2A.X and cleaved caspase-3-positive cells, and vascular endothelial growth factor-C and platelet and endothelial cell adhesion molecule 1-positive cells, respectively. AvidinOX is currently under clinical investigation to assess its use in delivering radioactive biotin to inoperable tumor lesions (ClinicalTrials. gov: NCT02053324 and NCT03188328). The present study further supported the potential clinical use of AvidinOX to target low bCet doses to inoperable tumor lesions, with or without an additional low dose of cisplatin. Since low doses of highly expensive monoclonal antibodies become effective with AvidinOX and low dose cisplatin, such therapies promise to be cheaper and less toxic than current treatments.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of intra‑tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer

Vesci

Carollo²,

Rosi

et al. 2019

Oncol Lett

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“…We also showed, in a mouse model, the use of this product for the targeting of radiolabeled biotin to inoperable neoplastic tissues, resulting in eradication of cancer lesions [3]. Tissue residence of AvidinOX was found to be dependent on the formation of Schiff's bases between avidin aldehyde groups, generated by sodium periodate oxidation of the sugar pyranosidic rings, and tissue protein amino groups.…”

Section: Introductionmentioning

confidence: 82%

“…Avidin (Tecnogen) was oxidized with 20mM sodium periodate (NaIO 4 ) (Sigma- Aldrich), in 100 mM acetate at pH 5.5 for 1 hour at room temperature, in the presence of a molar excess of 4-hydroxyazobenzene-2′-carboxylic acid (HABA) (Sigma-Aldrich) and purified by chromatography on a Sephadex G-25 fine desalting column (GE Healthcare) as previously reported [3]. Ovalbumin (Sigma-Aldrich), pentraxin 3 (PTX3) (Tecnogen), CEA (US biological) Tenatumomab (Sigma-Tau), Rituximab (Roche Pharma) and Herceptin® (Roche) were oxidized (without HABA) with periodate and purified by size exclusion chromatography as described above for avidin.…”

Section: Methodsmentioning

confidence: 99%

Chemical Linkage to Injected Tissues Is a Distinctive Property of Oxidized Avidin

et al. 2011

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We recently reported that the oxidized avidin, named AvidinOX®, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation.

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“…We also described the use of this product as a stable tissue artificial receptor for biotinylated drugs, like biotinylated cells or radiolabelled biotin [9]. Particularly, we showed in a mouse model the targeting of radiolabelled biotin to inoperable neoplastic tissues, resulting in eradication of cancer lesions [10]. Tissue residence of AvidinOX ® proved to be dependent on the formation of Schiff’s bases between avidin aldehyde groups, generated by sodium periodate oxidation of the sugar pyranosidic rings, and tissue protein amino groups.…”

mentioning

confidence: 99%

Preclinical Pharmacology and Safety of a Novel Avidin Derivative for Tissue‐Targeted Delivery of Radiolabelled Biotin

Petronzelli

Anastasi

Pelliccia

et al. 2011

Basic Clin Pharma Tox

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Abstract:We recently described an oxidized avidin variant, named AvidinOX Ò , which is a product that chemically links to tissue proteins while maintaining the capacity to uptake intravenously administered biotin. Such product proved to be successful in targeting radionuclide therapy in a mouse model of inoperable breast cancer. Here, we show that the uptake of a single or multiple doses of biotin (up to five times), by the tissue-bound AvidinOX Ò , is stable for 2 weeks. Taking into account that oxidized avidin is the first chemically reactive protein to be proposed for clinical use, we evaluated its tolerability, immunogenicity and mutagenicity. Present in vitro data indicate that AvidinOX Ò (up to 10 lg ⁄ 5 · 10 5 cells) does not affect cell viability or proliferation of PC3 human prostate cancer or 3T3 mouse fibroblast cell lines as well as primary mouse spleen cells. Safety pharmacology and toxicology studies were conducted using AvidinOX Ò up to the highest concentration compatible with its solubility (about 12 mg ⁄ mL), representing four times the product concentration intended for human use, and in the maximum administrable volume compatible with each study system. The intramuscular administration in rat and monkey induced a moderate to strong inflammatory response particularly after a second administration and consistently with the induction of an immune response. Interestingly, the intramuscular administration of AvidinOX Ò to rodents and monkeys exhibiting very high anti-avidin antibody titres was well tolerated with no systemic symptoms of any kind. Intravenous administration of AvidinOX Ò , performed to mimic an accidental injection of the dose intended for a local administration (15 lL of 3.3 mg ⁄ mL solution), showed significant localization of the product into the spleen not associated with uptake of the radiolabelled biotin intravenously injected after 24 hr, thus suggesting rapid inactivation. No mutagenic activity was induced by oxidized avidin in prokaryotic and eukaryotic cells. Overall, the present data indicate that AvidinOX Ò is well tolerated in rodents and nonhuman primates, thus supporting its clinical use within protocols of radionuclide therapy of inoperable tumour lesions.Recently, a novel pre-targeted interstitial radionuclide therapy, named intraoperative avidination for radionuclide treatment (IART Ò

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AvidinOX™ for Highly Efficient Tissue-Pretargeted Radionuclide Therapy

Cited by 20 publications

References 28 publications

Therapeutic efficacy of intra‑tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer

Therapeutic efficacy of intra‑tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer

Chemical Linkage to Injected Tissues Is a Distinctive Property of Oxidized Avidin

Preclinical Pharmacology and Safety of a Novel Avidin Derivative for Tissue‐Targeted Delivery of Radiolabelled Biotin

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