Photodynamic therapy of cancer, i.e. the generation of reactive oxygen species in the tumour environment which follows the irradiation of suitable photosensitising molecules, is an attractive modality for the selective ablation of inoperable superficial neoplastic lesions, such as certain head and neck, gastrointestinal, urogenital and gynecological tumours. It is likely that the scope and efficacy of photodynamic therapy could be enhanced by: - the availability of novel efficient photosensitizers which absorb at in the red / near infrared region of the spectrum, where light penetration of tissues is maximal - the use of antibody-photosensitizer conjugates or conceptually related innovative delivery systems, which concentrate the photosensitising molecules at suitable neoplastic sites.
The tumour neo-vasculature appears to be an attractive target, since the selective delivery of photosensitizers may occlude the tumour blood vessels, thus causing an avalanche of tumour cell deaths. In this Project, we have put together a network of academic research groups and companies, for the development of antibody-based targeted photodynamic therapy modalities. The planned research activity starts with the synthesis of novel photosensitising molecules suitable for conjugation to antibodies, and with the identification of novel human monoclonal antibodies, capable of a selective targeting of the tumour neovasculature for immuno-PDT applications.
Following an extensive in vitro characterization of the most promising antibody-photosensitizer conjugates (including an innovative delivery concept in which photosensitizers are non-covalently bound to the antibody), the therapeutic potential of the best conjugates will be tested in rodent models of cancer, paving the way to future clinical applications. Some of the members of our network have collaborated before, and have brought three antibody derivatives into advanced clinical and industrial development in the oncology field.
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