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Tumour Targeting Laboratory

Laboratory overview

We focus on the targeting and molecular imaging of tumours, as well as 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 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.

Our team of scientists and clinicians move between the laboratory and the bed side every day. We are uniquely positioned to develop treatments that benefit cancer patients. Prof. Andrew Scott, Head, Tumour Targeting Laboratory
TumourTargetting_31_01_2019-13 180315 ONJCRI TT 0087 180315 ONJCRI TT 0053

Our focus

EGFR targeting

We have identified a new class of conformationally exposed ErbB receptor epitopes, which has led to the characterization and development of mAb806, which targets EGFR expressed specifically in cancer cells and which 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 expanded to incorporate conducting structure-function studies of novel antibodies that target 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. Recent molecular engineering, structural and modelling approaches in our laboratory have defined novel Fc:FcRn and Fc:FcγR interactions, which 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, peptides and nanoparticles, both in preclinical models and more recently in clinical trials in cancer patients. These studies are showing encouraging results in patients with cancers of the brain, colon and breast, as well as other solid tumours.

Novel metabolic tracers

An exciting recent development in the molecular imaging of cancer comes from 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. Taking the discovery of novel metabolic tracers in the laboratory to clinical trials is a major focus of our molecular imaging / PET research program and 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. 33(24): 2585-2587, 2015.
  2. Burvenich IJ, Farrugia W, Lee FT, Catimel B, Liu Z, Makris D, Cao D, O'Keefe GJ, Brechbiel MW, King D, Spirkoska V, Allan LC, Ramsland PA, Scott AM. Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding human neonatal Fc receptor. MAbs. 2016 May-Jun;8(4):775-86.
  3. Gan HK, van den Bent M, Lassman AB, Reardon DA, Scott AM. Antibody-drug conjugates in glioblastoma therapy: the right drugs to the right cells. Nat Rev Clin Oncol. 2017 Nov;14(11):695-707
  4. Phillips AC, Boghaert ER, Vaidya KS, Falls HD, Mitten MJ, DeVries PJ, Benatuil L, Hsieh CM, Meulbroek JA, Panchal SC, Buchanan FG, Durbin KR, Voorbach MJ, Reuter DR, Mudd SR, Loberg LI, Ralston SL, Cao D, Gan HK, Scott AM, Reilly EB. Characterization of ABBV-221, a Tumor-Selective EGFR-Targeting Antibody Drug Conjugate. Mol Cancer Ther. 2018 Apr;17(4):795-805. 
  5. Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, Lehn S, Sjölund J, Reid S, Larsson C, Eriksson P, Anderberg C, Cortez E, Saal LH, Orsmark-Pietras C, Cordero E, Haller BK, Häkkinen J, Burvenich IJG, Lim E, Orimo A, Höglund M, Rydén L, Moch H, Scott AM, Eriksson U, Pietras K. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med. 2018 May;24(4):463-473.
  6. Li H, Zeitelhofer M, Nilsson I, Liu X, Allan L, Gloria B, Perani A, Murone C, Catimel B, Neville AM, Scott FE, Scott AM, Eriksson U. Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRα signalling in vivo. PLoS One. 2018 Jul 27;13(7):e0201089.  
For a complete list of Andrew Scott's publications, click here.

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