EX-VIVO PHAGE SEL. · Selection of phage displayed peptide and antibody libraries for specific binding to human tumour vascular by panning in ex vivo perfused human tumour-bearing organs

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Project objective

The main objective of the project is to generate antibodies that specifically bind to human tumour vasculature. This will be achieved by ex vivo perfusion of surgically resected livers containing tumours, with phage display libraries. The phage display technology has already been applied successfully in in-vivo selection for tumour vasculature in mice. However, a disadvantage of this system is that while the tumour cells can be human, the vasculature is of mouse origin, and the human tumour vasculature antigens will differ. Selection of phage displayed antibodies by perfusion of tumour-bearing organs is novel because it will give direct access to living human tumour vasculature. Using resected human liver segments, we have established a perfusion system, and demonstrated that phage are delivered to the tumour vasculature as demonstrated by immunohistochemistry. To ensure the highest possible success rate in the perfusion-selections, we have characterised different phage display systems for display efficiency and optimised phage production protocols The selected antibodies will initially be investigated in established immunohistochemical assays, and subsequently tested for potential tumour vascular targeting using resected tumour-bearing organs in our perfusion system. The perfusion-selection of phage-display libraries described offers a unique opportunity to generate clinically relevant antibodies or peptides for anti-vascular cancer therapy and to identify important human tumour vascular antigens.

Original text from CORDIS.

Participants

• UNIVERSITY COLLEGE LONDON · LONDONCoordinatorUnited Kingdom

Links

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