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A comparative immunofluorescence analysis of three clinical-stage antibodies in head and neck cancer.

Schwager K, Villa A, Rösli C, Neri D, Rösli-Khabas M, Moser G - Head Neck Oncol (2011)

Bottom Line: On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19.Interestingly, some specimens exhibited striking differences in staining by the three antibodies.These results suggests that an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.

View Article: PubMed Central - HTML - PubMed

Affiliation: Philochem AG, ETH Zurich, Institute of Pharmaceutical Sciences, Zurich, Switzerland.

ABSTRACT

Background: The antibody-based targeted delivery of bioactive molecules to tumour vasculature is an attractive avenue to concentrate therapeutic agents at cancer sites, while sparing normal organs. L19, F8 and F16 are three fully human monoclonal antibodies, specific to splice isoforms of fibronectin and tenascin-C, which bind to sites of active tissue remodeling and which are currently in Phase I and II clinical trials as radio-immunoconjugates and immunocytokines in patients with cancer and arthritis.In this article, we report the first comparative analysis of expression patterns for the extra domains EDB and EDA of fibronectin and A1 of tenascin-C in both primary and metastatic head and neck cancer lesions.

Methods: We performed a comparative immunofluorescence analysis with the L19, F8 and F16 antibodies in 40 freshly frozen human head and neck cancer specimens.

Results: On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19. Interestingly, some specimens exhibited striking differences in staining by the three antibodies.

Conclusions: These results suggests that an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.

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Related in: MedlinePlus

Immunofluorescence staining of head and neck cancer samples. The expression patterns and intensities of the splice isoforms extra domain A (EDA) and extradomain B (EDB) of fibronectin and the A1 domain of tenascin C were detected with the antibodies F8, L19 and F16, respectively (shown in green). A co-staining with an anti-von Willebrand factor antibody that stains blood vessels (red) and Dapi (blue) was performed. Abbreviations: SCC: squamous cell carcinoma; PA: pleomorphic adenoma.
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Figure 1: Immunofluorescence staining of head and neck cancer samples. The expression patterns and intensities of the splice isoforms extra domain A (EDA) and extradomain B (EDB) of fibronectin and the A1 domain of tenascin C were detected with the antibodies F8, L19 and F16, respectively (shown in green). A co-staining with an anti-von Willebrand factor antibody that stains blood vessels (red) and Dapi (blue) was performed. Abbreviations: SCC: squamous cell carcinoma; PA: pleomorphic adenoma.

Mentions: The staining intensities of biotinylated derivatives of the L19, F8 and F16 antibodies in 40 frozen specimens of head and neck cancer were studied by three-colour immunofluorescence microscopy. The tissue series included tumours of the oral cavity, the pharynx and the larynx [table 1]. Primary benign lesions, malignant tumours as well as metastatic cancer specimens were analyzed. The three antibodies L19, F8 and F16 had comparable high affinities towards their cognate antigen and were used in identical concentrations. The KSF antibody, specific to hen egg lysozyme and with no known reactivity towards human antigens [11], was used as negative control (data not shown). Figure 1 shows representative immunofluorescence findings with the three antibodies (green) in different tumour sections. Cell nuclei were stained with DAPI (blue), while blood vessels were coloured in red using an anti-von Willebrand antibody. In most specimens, all three antibodies exhibited a diffuse stromal staining, similar to previously described patterns of fibronectin and tenascin-C expression [12,13]. Interestingly, some specimens exhibited striking differences in staining by the three antibodies [Figure 1]. This observation suggests that, while at least one of the three antibodies is generally capable of intensely staining a given tumour, an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.


A comparative immunofluorescence analysis of three clinical-stage antibodies in head and neck cancer.

Schwager K, Villa A, Rösli C, Neri D, Rösli-Khabas M, Moser G - Head Neck Oncol (2011)

Immunofluorescence staining of head and neck cancer samples. The expression patterns and intensities of the splice isoforms extra domain A (EDA) and extradomain B (EDB) of fibronectin and the A1 domain of tenascin C were detected with the antibodies F8, L19 and F16, respectively (shown in green). A co-staining with an anti-von Willebrand factor antibody that stains blood vessels (red) and Dapi (blue) was performed. Abbreviations: SCC: squamous cell carcinoma; PA: pleomorphic adenoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108933&req=5

Figure 1: Immunofluorescence staining of head and neck cancer samples. The expression patterns and intensities of the splice isoforms extra domain A (EDA) and extradomain B (EDB) of fibronectin and the A1 domain of tenascin C were detected with the antibodies F8, L19 and F16, respectively (shown in green). A co-staining with an anti-von Willebrand factor antibody that stains blood vessels (red) and Dapi (blue) was performed. Abbreviations: SCC: squamous cell carcinoma; PA: pleomorphic adenoma.
Mentions: The staining intensities of biotinylated derivatives of the L19, F8 and F16 antibodies in 40 frozen specimens of head and neck cancer were studied by three-colour immunofluorescence microscopy. The tissue series included tumours of the oral cavity, the pharynx and the larynx [table 1]. Primary benign lesions, malignant tumours as well as metastatic cancer specimens were analyzed. The three antibodies L19, F8 and F16 had comparable high affinities towards their cognate antigen and were used in identical concentrations. The KSF antibody, specific to hen egg lysozyme and with no known reactivity towards human antigens [11], was used as negative control (data not shown). Figure 1 shows representative immunofluorescence findings with the three antibodies (green) in different tumour sections. Cell nuclei were stained with DAPI (blue), while blood vessels were coloured in red using an anti-von Willebrand antibody. In most specimens, all three antibodies exhibited a diffuse stromal staining, similar to previously described patterns of fibronectin and tenascin-C expression [12,13]. Interestingly, some specimens exhibited striking differences in staining by the three antibodies [Figure 1]. This observation suggests that, while at least one of the three antibodies is generally capable of intensely staining a given tumour, an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.

Bottom Line: On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19.Interestingly, some specimens exhibited striking differences in staining by the three antibodies.These results suggests that an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.

View Article: PubMed Central - HTML - PubMed

Affiliation: Philochem AG, ETH Zurich, Institute of Pharmaceutical Sciences, Zurich, Switzerland.

ABSTRACT

Background: The antibody-based targeted delivery of bioactive molecules to tumour vasculature is an attractive avenue to concentrate therapeutic agents at cancer sites, while sparing normal organs. L19, F8 and F16 are three fully human monoclonal antibodies, specific to splice isoforms of fibronectin and tenascin-C, which bind to sites of active tissue remodeling and which are currently in Phase I and II clinical trials as radio-immunoconjugates and immunocytokines in patients with cancer and arthritis.In this article, we report the first comparative analysis of expression patterns for the extra domains EDB and EDA of fibronectin and A1 of tenascin-C in both primary and metastatic head and neck cancer lesions.

Methods: We performed a comparative immunofluorescence analysis with the L19, F8 and F16 antibodies in 40 freshly frozen human head and neck cancer specimens.

Results: On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19. Interestingly, some specimens exhibited striking differences in staining by the three antibodies.

Conclusions: These results suggests that an individualized treatment procedure (e.g., choice of L19, F8 or F16 based on immuno-PET or immunofluorescence procedure) may represent the most logical avenue for offering the best possible antibody to any given patient.

Show MeSH
Related in: MedlinePlus