Novel ADC targets & Monoclonal Antibodies for Biopharmaceuticals
Therapeutic antibodies are the largest class of biopharmaceuticals for human disease. Development of more effective therapeutic strategies for cancers of high unmet need requires the continued discovery of disease specific cell surface protein targets for such therapeutic antibody targeting. Antibody Drug Conjugates (ADCs) are an emerging class of therapeutics which offer a potentially new way to treat cancer by combining the tumour-specific targeting of MAbs with the efficacy of cytotoxic drugs to maximise anti-cancer potency and minimise the drug’s exposure in normal tissues. ADCs currently account for around 15% of the clinical-stage anticancer antibody-based pipeline outnumbering bi-specific antibodies and fragments. Our research aims to identify new ADC drug targets for cancer with a focus on those cancer types which urgently require more effective therapeutic strategies to improve patient oucome. This research programme is facilitated through a number of clinical collaborators (St. Vincent’s University Hospital, Mater Hospital, Royal Victoria Eye & Ear Hospital).
This research programme is focused on:
Identification and investigation of novel membrane protein targets in colon, pancreatic, melanoma and breast cancer that show high cancer specific expression with limited expression in normal (in particular highly proliferating) tissues that maybe amenable to therapeutic antibody targeting using ADCs.
Development of functional anti-invasive blocking antibodies using functional hybridoma screening approaches
Identification of MAb target antigens and target binding partners by Immunoprecipitation/ proteomic analysis with the aim of identifying novel proteins associated with cancer invasion/ metastasis and drug resistance which may represent potential drug targets.
Contact
Martin Clynes (martin.clynes@dcu.ie)
Anne-Marie Larkin (anne-marie.larkin@dcu.ie)
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Publications
- Joyce H, McCann A, Clynes M, Larkin A. (2015) Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism. Expert Opin Drug Metab Toxicol. 2015 Apr 2:1-15. [Epub ahead of print].
- O’Sullivan D, Henry M, Joyce H, Dowling P, Mc Auley E, Walsh N, Barnham P, Clynes M, Larkin A. (2014) 7B7: A novel antibody directed against the Ku70/80 heterodimer blocks invasion in Lung squamous and pancreatic cancer cells. Tumour biology 2014 Apr 18.
- Walsh N, Kennedy S, Larkin AM, Tryfonopoulos D, Eustace AJ, Mahgoub T, Conway C, Oglesby I, Collins D, Ballot J, Ooi WS, Gullo G, Clynes M, Crown J, O'Driscoll L. (2010) Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis. Br J Cancer. 2010 Mar 30;102(7):1157-62. doi: 10.1038/sj.bjc.6605590.
- Larkin A, Moran E, Kennedy SM, Clynes M. (2005) Monoclonal antibody 5C3 raised against formalin fixed paraffin-embedded invasive breast tumour tissue: characterisation of its reactive antigen via immunoprecipitation and internal sequencing. J Immunol Methods. 2005 Aug;303(1-2):53-65.
