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CRISPR/Cas9 genome-wide screening for identification of therapeutic monoclonal antibody targets against tumour associated macrophages

Junghus, Fredrik (2020) MOBN02 20192
Degree Projects in Molecular Biology
Popular Abstract
Identifying new targets for cancer treatments

Cancer continues to be one of the leading causes of mortality worldwide, responsible for millions of deaths each year. As our knowledge regarding the biological systems involved has grown, incredible progress has been made towards the development of effective new treatments. We now know that targeting of cells responsible for promoting cancer growth can result in remarkable improvements in patient outcomes. One area of increasing relevance in this field is the role macrophages play in cancer progression and severity.

Macrophages are a type of white blood cell which engulf and destroy invading pathogens. Targeting macrophages within tumours provides a new avenue for the development of... (More)
Identifying new targets for cancer treatments

Cancer continues to be one of the leading causes of mortality worldwide, responsible for millions of deaths each year. As our knowledge regarding the biological systems involved has grown, incredible progress has been made towards the development of effective new treatments. We now know that targeting of cells responsible for promoting cancer growth can result in remarkable improvements in patient outcomes. One area of increasing relevance in this field is the role macrophages play in cancer progression and severity.

Macrophages are a type of white blood cell which engulf and destroy invading pathogens. Targeting macrophages within tumours provides a new avenue for the development of cancer treatments. Therapeutic lab made antibodies provide an excellent basis for such treatments due to their incredible target specificity reducing unwanted side effects and their utilisation of the patient’s own immune system. Currently, an issue with developing such antibodies is our lack of knowledge about targets and their specific roles in cancer. A technique to overcome this involves the creation of antibody libraries which bind to a wide range of targets. Candidates from these libraries can be selected for further development based upon their effects on cancer cells. A problem with this approach is the difficulty in verifying the specific target to which the candidate antibodies bind. Current approaches for this are incredibly expensive and generally have very low success rates.

This study demonstrated an effective new technique for determining unknown targets to which therapeutically viable antibodies bind. The technique was used to identify the binding targets of eight new candidate antibody therapeutics which bind to cancer-causing macrophages and either destroy them or activate their tumour killing ability. The technique utilises a population of cells which each have a different gene removed. The cells are treated with the candidate antibody which contains a fluorescent label and then sorted using a machine. Cells to which the antibody does not bind have had the gene for the target removed. DNA from these cells can be extracted and sequenced to determine the target to which the antibody binds. A summary of the technique can be seen in the image.

In this study targets for all eight candidate antibodies were identified. A number of the these currently have no treatments targeted against them and present exciting opportunities for new cancer therapeutics.

Master’s Degree Project in Molecular Biology 45 credits 2020
Department of Biology, Lund University
Advisor: Björn Nilsson
Division of Haematology and Transfusion Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Junghus, Fredrik
supervisor
organization
course
MOBN02 20192
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9008833
date added to LUP
2020-05-19 13:35:00
date last changed
2020-05-19 13:35:00
@misc{9008833,
  author       = {Junghus, Fredrik},
  language     = {eng},
  note         = {Student Paper},
  title        = {CRISPR/Cas9 genome-wide screening for identification of therapeutic monoclonal antibody targets against tumour associated macrophages},
  year         = {2020},
}