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Testing and validation of bispecific antibody combinations targeting treatment-resistant cancer stem cells using organoid-based screening tools: a new drug discovery paradigm

Objective

Colorectal cancer (CRC) was diagnosed in 1.23 million people worldwide (EU 333,000) in 2008 and 608,000 (EU 148,000) died of the disease. While some new treatments have been advanced in CRC many have failed clinical testing; metastatic CRC is still largely incurable.
In CRC, Cancer Stem Cells (CSC) are responsible for tumour progression and resistant to standard chemotherapies. The Wnt signal transduction cascade controls normal colon physiology but also CSC maintenance. Deregulation of Wnt and other mitogenic pathways results in formation of aggressive tumours with metastatic potential. Novel combinatorial drugs targeting CSCs are required to address signalling redundancy and subvert resistance and escape mechanisms. However to test them effectively better drug screening tools must be developed. The high failure rate in cancer drug research has been linked to the poor predictive capacity of drug screening models for cancer and the inability to select the right patients for treatment.
In SUPPRESSTEM, novel antibody-based therapeutics will be designed to modulate the Wnt pathway externally in combination with mitogenic receptors resulting in specific inhibition of CSCs with minimal toxicity on healthy tissue. The likelihood of clinically translating these goals will be enhanced because testing will be performed on relevant human patient material (both tumour and normal) using organoid technology and novel imaging readouts. In depth analysis of the phenotype of responsive organoids (patient material) will be used to identify a lead product.
Successful execution of SUPPRESSTEM will provide an innovative drug product and drug screening tool ready for clinical validation that ultimately will increase the life expectancy and quality of cancer patients. Funding of SUPPRESSTEM will enable three research-focused SME’s to establish an innovative drug discovery paradigm with broad application in the cancer drug development.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/basic medicine/physiology
  • /medical and health sciences/clinical medicine/oncology/cancer/colorectal cancer

Call for proposal

FP7-HEALTH-2013-INNOVATION-2
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

MERUS BV
Address
Padualaan 8 133
3584CH Utrecht
Netherlands
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 3 229 540,60
Administrative Contact
Shelley Margetson (Ms.)

Participants (4)

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Netherlands
EU contribution
€ 1 122 911
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam
Activity type
Other
Administrative Contact
Don Van Velzen (Mr.)
OCELLO BV
Netherlands
EU contribution
€ 892 151
Address
J.h Oortweg 21
2333 CH Leiden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Leo Price (Dr.)
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Spain
EU contribution
€ 338 346,80
Address
Carrer Baldiri Reixac 10-12 Parc Scientific De Barcelona
08028 Barcelona
Activity type
Research Organisations
Administrative Contact
Raquel Furio (Ms.)
GENOME RESEARCH LIMITED
United Kingdom
EU contribution
€ 370 369,60
Address
The Gibbs Building, Euston Road 215
NW1 2BE London
Activity type
Research Organisations
Administrative Contact
David Davison (Mr.)