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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

Analysis of staining intensities. Comparison of staining intensities obtained with the antibodies F8, L19 and F16 in A) primary tumours and metastasis tumour samples and in B) primary benign and primary maligant tumour specimens. C) Average staining intensities of tumours of the oral cavity, the pharynx or the larynx. Standard Errors of the Mean of scoring values are displayed.
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Figure 2: Analysis of staining intensities. Comparison of staining intensities obtained with the antibodies F8, L19 and F16 in A) primary tumours and metastasis tumour samples and in B) primary benign and primary maligant tumour specimens. C) Average staining intensities of tumours of the oral cavity, the pharynx or the larynx. Standard Errors of the Mean of scoring values are displayed.

Mentions: Figure 2 presents a semi-quantitative analysis of staining intensities of L19, F8 and F16, ranging from 0 (absent), to 3 (+++). Independent investigators assessed all pictures, assigning a scoring intensity to each specimen. The average of these values and the corresponding standard error were displayed in the figure. Primary tumours and metastatic tumour lesions as well as primary benign and malign tumours were analyzed, as well as tumour samples from different anatomical locations (oral cavity, larynx and pharynx). On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19. As a consequence, armed antibodies based on F8 or F16 may represent the best choice for the treatment of head and neck cancer, whereas L19 may be more appropriate for other cancer types which strongly express the EDB domain of fibronectin (e.g., kidney cancer; [7]). However, it cannot be excluded that the weaker staining observed for EDB may be a consequence of lower stability of this antigen, which has been reported in case of tissue section storage at -80°C for longer than 20 days [14]. In a previous study, a radioiodinated version of the L19 antibody has been tested in scFv format in a small immunoscintigraphic clinical study in patients with head and neck squamous cell carcinomas. Successful targeting of the primary tumour could be achieved in 4 out of 5 patients [9]. Further imaging studies are needed to reveal whether targeting of F16 and F8 is superior to L19 in head and neck cancer patients. Indeed, two Phase II clinical trials with SIP(L19) [6] and SIP(F16) labelled with 124I [15] are currently being performed.


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)

Analysis of staining intensities. Comparison of staining intensities obtained with the antibodies F8, L19 and F16 in A) primary tumours and metastasis tumour samples and in B) primary benign and primary maligant tumour specimens. C) Average staining intensities of tumours of the oral cavity, the pharynx or the larynx. Standard Errors of the Mean of scoring values are displayed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Analysis of staining intensities. Comparison of staining intensities obtained with the antibodies F8, L19 and F16 in A) primary tumours and metastasis tumour samples and in B) primary benign and primary maligant tumour specimens. C) Average staining intensities of tumours of the oral cavity, the pharynx or the larynx. Standard Errors of the Mean of scoring values are displayed.
Mentions: Figure 2 presents a semi-quantitative analysis of staining intensities of L19, F8 and F16, ranging from 0 (absent), to 3 (+++). Independent investigators assessed all pictures, assigning a scoring intensity to each specimen. The average of these values and the corresponding standard error were displayed in the figure. Primary tumours and metastatic tumour lesions as well as primary benign and malign tumours were analyzed, as well as tumour samples from different anatomical locations (oral cavity, larynx and pharynx). On average, F8 and F16 exhibited similar staining intensities, which were typically stronger than L19. As a consequence, armed antibodies based on F8 or F16 may represent the best choice for the treatment of head and neck cancer, whereas L19 may be more appropriate for other cancer types which strongly express the EDB domain of fibronectin (e.g., kidney cancer; [7]). However, it cannot be excluded that the weaker staining observed for EDB may be a consequence of lower stability of this antigen, which has been reported in case of tissue section storage at -80°C for longer than 20 days [14]. In a previous study, a radioiodinated version of the L19 antibody has been tested in scFv format in a small immunoscintigraphic clinical study in patients with head and neck squamous cell carcinomas. Successful targeting of the primary tumour could be achieved in 4 out of 5 patients [9]. Further imaging studies are needed to reveal whether targeting of F16 and F8 is superior to L19 in head and neck cancer patients. Indeed, two Phase II clinical trials with SIP(L19) [6] and SIP(F16) labelled with 124I [15] are currently being performed.

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