HER Imaging and Molecular Interaction Mapping in Breast Cancer
FP7 imagint
 
   Partner: University College London

Project Leader
Kerry Chester

Group members
Berend Tolner
Bride Foster
Gaurav Bhavsar
Leah Ensell
Maria Livanos
Robert Goldstein



Selected publications
Tolner B, Bhavsar G, Foster B, Vigor K and Chester KA (2012) Chapter-37: Production of Recombinant Proteins from Pichia pastoris: Interfacing Fermentation and Immobilized Metal Ion Affinity Chromatography, In: Laboratory Protocols in Fungal Biology; (Eds.) Gupta, V.K., Tuohy, M., Manimaran, A., Turner, K. and Ovonvan, A. Springer Science & Business Media, LLC, 233 Spring Street, New York, NY 10013, USA.

Andrady C, Sharma SK, Chester KA (2011) Antibody-enzyme fusion proteins for cancer therapy. Immunotherapy 3:193-211. Review. Pubmed

Marsh D, Suchak K, Moutasim KA, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette SM, Weinreb PH, Chester KA, Chana JS, Marshall JF, Hart IR, Hackshaw AK, Piper K, Thomas GJ (2011) Stromal features are predictive of disease mortality in oral cancer patients. J Pathol 223:470-81. Pubmed

Vigor KL, Kyrtatos PG, Minogue S, Al-Jamal KT, Kogelberg H, Tolner B, Kostarelos K, Begent RH, Pankhurst QA, Lythgoe MF, Chester KA (2010) Nanoparticles functionalized with recombinant single chain Fv antibody fragments (scFv) for the magnetic resonance imaging of cancer cells. Biomaterials 31:1307-15. Pubmed

Meyer T, Gaya AM, Dancey G, Stratford MR, Othman S, Sharma SK, Wellsted D, Taylor NJ, Stirling JJ, Poupard L, Folkes LK, Chan PS, Pedley RB, Chester KA, Owen K, Violet JA, Malaroda A, Green AJ, Buscombe J, Padhani AR, Rustin GJ, Begent RH (2009) A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas. Clin Cancer Res 15:4484-92. Pubmed

 
Introduction

Our research goal is to use antibodies, fragments thereof or antibody-like frameworks (DARPins) as a base for medicines to be used for imaging and therapy of cancer. The antibody fragments we use consist of the smallest antibody segment (scFv) that recognises the target (antigen).

Figure - Molecular model of MFE23. MFE-23, our most characterised scFv, reacts with CEA and was the first scFv to target cancers in man.

We focus on design and construction of these molecules and their interaction with cancer targets. Our primary cancer targets are the epidermal growth factor receptor family (EGFR) for breast /brain cancers; carcinoembryonic antigen (CEA) which is a glycoprotein expressed in colorectal adenocarcinomas; and the avß6 integrin which is present on head and neck cancers.

A strong translational theme is central to our research thinking. We aim to bring the therapeutics designed by our team from bench to bed side. To facilitate this process, the group has a dedicated facility which can produce clinical grade microbial-expressed recombinant proteins in compliance with Good Manufacturing Practice (GMP).

The group has a developmental laboratory which harbours equipment similar to that in the GMP clean rooms. This layout simplifies throughput from developmental to GMP production stage of a lead molecule.

To date some 150 GMP batches have been produced, using the yeast Pichia pastoris as a production platform. The facility, the UCL Cancer Institute Research Trust GMP Facility (CIRT GMP Facility) generates so-called investigational medicinal products (IMPs) for early phase trials. The site is licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) to produce these IMPs.

Role of UCL within the “Imagint Consortium”

Our part in IMAGINT is the production of seed lots and subsequent production of GMP compliant 'Imagint'-therapeutics. Furthermore, the clinical phase I trial will be performed by UCL.




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