| IDENTIFICATION
OF NOVEL TARGETS OVEREXPRESSED ON THE CELL SURFACE OF
HUMAN PROSTATE TUMOUR CELLS.
Dr Tahereh Kamalati Imperial College London, Department of Oncology |
 |
The majority of prostate tumours arise from prostate epithelial cells. The aim of this project is to generate "tools" to the "cell surface" of human prostate epithelial cells for better "detection" of these tumour cells, in patients. The reason we are interested in this is that such "tools", currently do not exist and once made, would be invaluable for detection of prostate tumours as well as for targeting these tumours with toxic drugs with out affecting the rest of the body.
The tools we have generated are called "antibodies". The reason we are keen to make antibodies as tools is that antibodies are naturally occurring proteins, which are made by the human body as a part of its defence system. We have made human antibodies specifically for use in human patients, so that once injected in to the patient, they do not elicit an adverse reaction.
We have used a technique called Phage Display to develop our human antibodies in the laboratory. In doing this, we have developed 15 individual antibodies to the cell surface of live human prostate epithelial cells. Comparison of these antibodies with all the already existing antibodies shows that our 15 antibodies have not been described before and are therefore unique.
In studying these, we have found that two of our antibodies called scFv 95.2 and scFv 98.1 can identify and react with normal human prostate epithelial cells. Additionally, both of these antibodies show significantly more reactivity with human prostate tumour cells in comparison to normal prostate epithelial cells. This suggests that these antibodies have therapeutic applications in detecting and targeting prostate cancer cells. In this context, these antibodies may be good 'tools' for the detection of human prostate tumours in patient tissue samples. Additionally and importantly, these antibodies may be useful for detecting prostate tumour cells in patients, especially when they have spread to other organs. In this light, these antibodies could also be used to target toxic medicines directly to the tumour in patients in order to eradicate the tumour with out affecting the rest of the body.
Further, although we do not yet know the target that these antibodies recognise and bind to on the cell surface of tumour cells, by studying the reactivity of our antibodies with prostate tumour cells in the laboratory, we have established that the target for these antibodies are not one of the known, prostate specific cell surface proteins previously reported and are therefore unique.
Having shown that these antibodies recognise human prostate tumour tissues efficiently, in this proposal, we seek funding to identify the target molecules that these antibodies react with on the cell surface of human prostate tumour cells. This will help further development of these antibodies as therapeutics for targeting prostate tumour cells in patients. We aim to identify the target molecules of these antibodies on the cell surface of prostate tumour cells by breaking the cells up in special chemicals that will preserve their reactivity and separating the components of the tumour cells according to size and reacting it with the antibodies. This will identify the target molecule's molecular weight. Subsequently, this information will be used to identify the target molecules in a repeat experiment, isolate this component and use a special technique (Sequencing) to identify the building blocks (amino acids) that the target molecule is made of. The sequence of the amino acids that these targets are made up from can then be used to search libraries of amino acid sequences (protein sequence data bases) and hence identify the molecule.
We already have the expertise, methodology and equipment for doing this in our laboratories. We now seek funding for a Research Assistant to help us carry out this work.
Interim Progress Report
can be viewed
here, (in .pdf format).
Progress report, 01 May 2008.
Project 2006/10