140904-jamesbraund-0716

Tumour targeting

Laboratory overview

We focus on the targeting and molecular imaging of tumours and exploring receptor-based signaling pathways responsible for cancer cell growth.  Through the development of innovative strategies for molecular imaging of cancer, and identifying cellular targets suitable for antibody therapy, we are developing new cancer therapies, with a particular focus on targeting of cancer cells with novel recombinant antibodies. In addition to pursuing clinical trials of novel antibodies, small molecules and imaging ligands, we are exploring mechanisms of clinical resistance to tumour targeting agents.

Everyday our team of scientists and clinicians move between the laboratory and the bed side. We are uniquely positioned to develop treatments that benefit cancer patients. Prof. Andrew Scott. Head, Tumour Targeting Laboratory
TumourTargeting-1400x900_4 140404-jamesbraund- 1588 140904-jamesbraund-0984

Our focus

EGFR targeting

We have identified a new class of conformationally exposed ErbB receptor epitopes that led to the characterization and development of mAb806, which targets EGFR expressed specifically in cancer cells and uniquely causes signalling abrogation and altered EGFR processing. These findings have provided a new paradigm in antibody-based targeting and therapy of solid tumours. This work has extended to structure-function studies of novel antibodies targeting cell surface receptors expressed in tumours, investigating mechanisms of resistance to ErbB targeting agents, and targeting key molecules involved in sustaining the tumour microenvironment.

Antibody humanisation

We have developed techniques for generation and humanisation of antibodies, and recent molecular engineering, structural and modelling approaches in our laboratory have defined novel Fc:FcRn and Fc:FcγR interactions that result in improved immune effector function and bioavailability of humanised antibodies. We have also developed strategies to deliver payloads specifically to tumours through conjugation of siRNA, toxins and isotopes to recombinant antibodies, and nanoparticles, both in preclinical models and more recently in clinical trials in cancer patients. These studies are showing encouraging results in patients with brain cancer, colon cancer and head and neck cancer.

Novel metabolic tracers

An exciting development in molecular imaging of cancer is the identification of critical biochemical pathways that are responsible for tumour growth and metastasis, which can be imaged with novel SPECT and positron emission tomography (PET) tracers. Extending the laboratory discoveries of novel metabolic tracers into clinical trials is a major focus of our molecular imaging / PET research program, and which is leading to a deeper understanding of tumour biology and therapy response.

 

 

Quick Facts

What is an antibody?

An antibody is an immune protein produced because of the introduction of a foreign substance into the body. It is the antibody's job to eliminate the foreign substance from the body by alerting the immune system to act.

How can an antibody target cancer?

Cancer scientists are able to develop and introduce antibodies into the body. These antibodies can be designed to recognise and target a specific feature of the tumour with the objective of inhibiting or stopping tumour growth. 

What are PET, MRI and SPECT?

Molecular imaging technologies which allow researchers to see whether treatments are effectively targeting a tumour.

1. Ciprotti, M., N.C. Tebbutt, F.T. Lee, S.T. Lee, H.K. Gan, D.C. McKee, G.J. O'Keefe, S.J. Gong, G. Chong, W. Hopkins, B. Chappell, F.E. Scott, M.W. Brechbiel, A.N. Tse, M. Jansen, M. Matsumura, M. Kotsuma, R. Watanabe, R. Venhaus, R.A. Beckman, J. Greenberg, and A.M. Scott,Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer. J Clin Oncol, 2015. Jun 29. pii: JCO.2014.60.4256. [Epub ahead of print]

2. Reilly, E.B., A.C. Phillips, F.G. Buchanan, G. Kingsbury, Y. Zhang, J.A. Meulbroek, T.B. Cole, P.J. DeVries, H.D. Falls, C. Beam, J. Gu, E.L. Digiammarino, J.P. Palma, C.K. Donawho, N.C. Goodwin, and A.M. Scott, Characterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody. Mol Cancer Ther, 2015. 14(5): p. 1141-51.

3. Dingjan, T., I. Spendlove, L.G. Durrant, A.M. Scott, E. Yuriev, and P.A. Ramsland, Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies. Mol Immunol, 2015. 67: p. 75-88.

4. Vail, M.E., C. Murone, A. Tan, L. Hii, D. Abebe, P.W. Janes, F.T. Lee, M. Baer, V. Palath, C. Bebbington, G. Yarranton, C. Llerena, S. Garic, D. Abramson, G. Cartwright, A.M. Scott, and M. Lackmann, Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment. Cancer Res, 2014. 74(16): p. 4470-81.

5. Burvenich, I.J., F.T. Lee, G.A. Cartwright, G.J. O'Keefe, D. Makris, D. Cao, S. Gong, A.C. Chueh, J.M. Mariadason, M.W. Brechbiel, R.A. Beckman, K. Fujiwara, R. von Roemeling, and A.M. Scott, Molecular Imaging of Death Receptor 5 Occupancy and Saturation Kinetics In Vivo by Humanized Monoclonal Antibody CS-1008. Clin Cancer Res, 2013. 19(21): p. 5984-93.

Meet our team

Study at ONJCRI

Learn more