P104 Radioimmunotherapy of Head and Neck Cancer Xenografts Using 131I-L19-SIP for Selective Targeting of Tumor Vasculature

Tijink, Bernard M.; Neri, Dario; Budde, Marianne; Leemans, C. René; Dinkelborg, Ludger; Walsum, Marijke Stigter-van; Zardi, Luciano; Dongen, Guus A.M.S. van

doi:10.1001/archotol.132.8.886-a

Cited by 53 publications

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“…Interestingly, Tijink et al (2006) also demonstrated maximum localisation of 131 I-L19-SIP (8.6 %ID g À1 ) in FaDu head and neck tumours at 24 h. Although higher radiolabelled antibody levels were found in blood at 3 h in the SW1222 tumour model, this fell dramatically by 24 and 72 h post-injection, indicating good blood clearance and produced high tumour to normal tissue ratios. Indeed, at 24 h, tumour to blood ratio was 28 : 1 (Table 2).…”

Section: Discussionmentioning

confidence: 87%

“…Berndorff et al (2005) reported that a single injection of 74 MBq 131 I-L19-SIP to F9 tumour-bearing mice resulted in a 10-day tumour growth delay and a median survival of 22 days; 13 days longer than that of control mice. More recently, Tijink et al (2006) also demonstrated that a single dose of 74 MBq 131 I-L19-SIP caused a maximum reduction in FaDu tumour size at day 18. However, at day 26, these tumours had re-grown to their initial size.…”

Section: Discussionmentioning

confidence: 89%

“…Borsi et al (2002), also demonstrated maximum localisation of the 125 I-L19-SIP, 6.1 %ID g À1 , at 6 h in the SK-MEL-28 melanoma tumour-bearing mice, with tumour to blood ratios of 1.22 at this time point. More recently, using FaDu head and neck cancer xenograft-bearing mice, Tijink et al (2006), have also demonstrated maximum tumour localisation of 125 I-L19-SIP antibody at 6 h post-injection.…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, several radiolabelled derivatives of the L19 antibody have been studied in biodistribution experiments as well as being evaluated in clinical radioimmunscintigraphy studies (Santimaria et al, 2003). Biodistribution experiments and RIT studies with the L19-SIP antibody have been carried out in tumour-bearing mice and rats, and have demonstrated selective localisation in different tumour models, for example, human melanomas, mouse embryonal teratocarcinomas, human head and neck squamous cell carcinomas, and rat gliomas Berndorff et al, 2005;Spaeth et al, 2006;Tijink et al, 2006). Finally, the therapeutic potential of 131 I-L19-SIP is currently being investigated in clinical trials in Italy and Switzerland (Kaspar et al, 2006).…”

mentioning

confidence: 99%

“…I-labelling Preparation of 131 I-L19-SIP for therapy was performed according to the 'IODO-GEN-coated MAb method' (Visser et al, 2001;Tijink et al, 2006). Briefly, 131 I (444 MBq) was added to a glass vial in 1 ml NaOH (1 mmol l À1 ), after which 10 ml of ascorbic acid (1.4 mg ml À1 ) was added.…”

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confidence: 99%

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Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

et al. 2007

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Angiogenesis is a characteristic feature of tumours and other disorders. The human monoclonal antibody L19-SIP targets the extra domain B of fibronectin, a marker of angiogenesis expressed in a range of tumours. The aim of this study was to investigate whole body distribution, tumour localisation and the potential of radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours. Two colorectal tumour models with highly different morphologies, the SW1222 and LS174T xenografts, were used in this study. Localisation and retention of the L19-SIP antibody at tumour vessels was demonstrated using immunohistochemistry and Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models were carried out with 125 I-labelled L19-SIP. Finally, 131 I-labelled antibody was used to investigate the potential of radioimmunotherapy in SW1222 tumours. Using immunohistochemistry, we confirmed extra domain B expression in the tumour vasculature. Immunofluorescence demonstrated localisation and retention of injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels. Biodistribution studies using a 125 I-labelled antibody showed selective tumour uptake in both models. Higher recorded values for localisation were found in the SW1222 tumours than in the LS174T (7.9 vs 6.6 %ID g À1 ), with comparable blood clearance for both models. Based on these results, a radioimmunotherapy study was performed in the SW1222 xenograft using 131 I-Labelled L19-SIP (55.5 MBq), which showed selective tumour uptake, tumour growth inhibition and improved survival. Radio-and fluorescence-labelled L19-SIP showed selective localisation and retention at vessels of two colorectal xenografts. Furthermore, 131 I-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

et al. 2007

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Targeted radionuclide therapy in head and neck cancer

Nestor

2010

Head & Neck

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There is great potential for targeted radionuclide therapy (TRT) in the treatment of head and neck cancer. In recent years, developments in fields such as antigen screening, protein engineering, and cancer biology have facilitated the rational design of targeted pharmaceuticals, with monoclonal antibodies forming the most rapidly expanding category. TRT may be a promising way to improve targeted treatment, especially in head and neck cancer, because of the intrinsic radiosensitivity of this tumor type. TRT may also provide a good foundation on which to build rational biologic combination therapies. In the next few years the use of TRT may offer new opportunities for further improvement of the therapeutic ratio that potentially may obviate or reduce the need for conventional cytotoxics.

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A high‐affinity human monoclonal antibody specific to the alternatively spliced EDA domain of fibronectin efficiently targets tumor neo‐vasculature in vivo

Villa

Trachsel

Kaspar

et al. 2008

Intl Journal of Cancer

224

312

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The alternatively spliced extra-domain B of fibronectin is one of the best characterized markers of tumor angiogenesis. Similarly, the extra-domain A (EDA), which can also be inserted in the fibronectin transcript by a mechanism of alternative splicing, has been shown to preferentially accumulate around new blood vessels in certain tumors, but this antigen has not been investigated so far as a target for antibody-based biomolecular intervention. We here describe the generation of 3 human monoclonal antibodies (named F8, B7 and D5), which recognize the same epitope of EDA, but which differ in terms of their dissociation constant to the human antigen (K D 5 3.1, 16 and 17 nM, measured for monomeric preparations of the F8, B7 and D5 antibodies, respectively, in recombinant scFv format). When the 3 antibody fragments were cloned and expressed with a 5 amino acid linker, the 3 resulting homodimeric antibody preparations displayed comparable tumor: organ ratios in quantitative biodistribution studies, performed in immunocompetent 129SvEv mice, bearing subcutaneous syngeneic F9 murine tumors. The percent injected dose per gram (%ID/g) values in tumors 24 hr after intravenous injection were 9.3, 10.2 and 13 for F8, B7 and D5, respectively. The F8 antibody may serve as useful building block for the development of antibody-based targeted anti-cancer therapeutics. Preclinical and clinical investigations are facilitated by the fact that F8 recognizes the human and mouse antigen with comparable affinity, and by the observation that EDA over-expression is detectable not only in solid tumors, but also in hematological malignancies.

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P104 Radioimmunotherapy of Head and Neck Cancer Xenografts Using 131I-L19-SIP for Selective Targeting of Tumor Vasculature

Cited by 53 publications

References 0 publications

Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

Targeted radionuclide therapy in head and neck cancer

A high‐affinity human monoclonal antibody specific to the alternatively spliced EDA domain of fibronectin efficiently targets tumor neo‐vasculature in vivo

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