Abstract
BackgroundThe 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.MethodsWe performed a comparative immunofluorescence analysis with the L19, F8 and F16 antibodies in 40 freshly frozen human head and neck cancer specimens.ResultsOn 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.ConclusionsThese 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.
Highlights
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
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 (SCC), observing tumour localization in 4 of 5 patients [9]
Radioiodinated derivatives of both L19 and F16 antibodies in small immunoprotein format (SIP) format [5,10] have been studied in Phase II clinical trials in over 100 patients with cancer, including head and neck cancer patients [6] [unpublished results]
Summary
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. 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. The alternatively spliced extra domain A (EDA) and B (EDB) of fibronectin and A1 domain of tenascin-C represent three of the best-characterized markers of angiogenesis and have been reported to be expressed around the neo-vasculature and in the stroma of. 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 (SCC), observing tumour localization in 4 of 5 patients [9]. Radioiodinated derivatives of both L19 and F16 antibodies in SIP format [5,10] have been studied in Phase II clinical trials in over 100 patients with cancer, including head and neck cancer patients [6] [unpublished results]
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