07/H0308/249

Cambridgeshire 2 Research Ethics Committee

Domantis Ltd

Generating Therapeutic Domain Antibodies

Generating Therapeutic Domain Antibodies

Permission to publish contact details not yet received

Permission to publish contact details not yet received

Tissue blocks (paraffin or fresh frozen) for immunohistochemistry analysis. Fresh frozen tissue is stored at -70C due to its perishable nature and paraffin blocks can be kept at RT. All tissue types may be utilised. Primary human cells: myeloid, lymphoid, keratinocytes, epitheleal, endothelial, fibroblast, mesenchymal, endodermal, hemangioblastoid, and neuronal cells may be cultured for up to two weeks for in vitro assays then disposed of according to SOP's. The cells will be kept cryopreserved until used for the assays. The number of samples utilised will vary with each therapeutic dAb project.
The anonymised samples will be stored in secured designated freezers and fridges during the project and experimental procedures will take place in designated tissue culture facilities or laboratory areas. All human samples will be logged in and logged out with disposal on secured database and laboratory notebooks. All exploratory research data is recorded in Domantis laboratory notebooks (electronic and paper). The notebooks are countersigned by a qualified researcher to validate the scientific integrity of the data soon after entry into the notebooks. Research teams within the company will also review and critique the data.

Tissue blocks (paraffin or fresh frozen) for immunohistochemistry analysis. Frozen tissue is stored at -70C due to its perishable nature and paraffin blocks can be kept at RT. All tissue types may be utilised
The number of samples utilised will vary with each therapeutic dAb project.
All human samples will be logged in and logged out with disposal on secured database and laboratory notebooks. All exploratory research data is recorded in Domantis laboratory notebooks (electronic and paper). The notebooks are countersigned by a qualified researcher to validate the scientific integrity of the data soon after entry into the notebooks. Research teams within the company will also review and critique the data.

Therapeutic antibodies have become an important group of drugs for the treatment of a variety of disorders and seventeen have already been approved in the United States by the US Food and Drug Administration.
Domantis has developed libraries (100 billion) of fully human antibody fragments known as domain antibodies (dAbs). dAbs are unique in the following respects: they are robust well expressed proteins 1/13 the size of conventional antibodies, they can be easily engineered to hit multiple targets which enhances the ability to treat a multifaceted disease (e.g. autoimmune disease). dAbs can be administered systemically and also via the lung and orally unlike other protein therapeutics, which offers advantages in terms of ease of delivery.
dAbs represent the next generation of human therapeutic antibodies.
The main focus of research will be aimed at developing therapeutic dAbs to treat cancer, autoimmune diseases, inflammatory diseases and metabolic diseases (other disease process will also be considered).
The use of human tissue or cells for these studies is the most relevant towards the aim of understanding molecular mechanisms and identifying novel human dAbs for eventual clinical development.
In contrast the use of animal tissue is suboptimal in this respect and reduces the dependency on animals and animal derived material for these studies.
In order to characterise candidate therapeutic dAbs for clinical development the following experimental techniques may be utilised but are not limited to:
- culture of human cells or tissue in vitro for treatment with reagents (e.g. dAbs, biopharmaceuticals or chemicals) followed by evaluation of their effect on e.g. cell proliferation, cell death, analysis of cell surface markers by flow cytometry analysis of secreted proteins in the cell culture, RNA analysis
- screening to find the therapeutic candidate dAbs
- histological analysis on human tissue (disease and normal panels) to evaluate the specificity of the dAbs

No genetic testing, reproductive research or cell cloning will be undertaken.

Anonymised primary human cells or tissue from disease patients and appropriate controls will be obtained from approved suppliers.
Informed consent will be obtained by the approved supplier. A general consent form will be available for inspection from each approved supplier. The commercial supplier will be paid for purchase of the human material.
Donor blood cells may also be obtained via the GSK donor panel (Hertfordshire LREC approved).
Results of in vitro research studies may be shared with other groups of the GSK organisation of which Domantis is part of. No data will include identification of research participants as the original samples are anonymised. The data gained from the research may be published in peer reviewed journals or presented at scientific meetings.

In general research will be aimed at cancer, autoimmune disease, inflammatory diseases and metabolic diseases although other disease areas may be considered.
The research will involve identification of candidate theraputic human domain antibodies (dAbs) from a number of different in vitro assays. For example dAbs to a specific haematological cancer cell surface marker maybe tested for specificity on normal human lymphoid cells and/or tissue blocks.
None of the research is related to the testing or safety of cosmetics or other consumer products.

Favourable Opinion

not yet recieved