Canine Immunotherapeutics
Lead Research Organisation:
University of Edinburgh
Department Name: Edinburgh Cancer Research Centre
Abstract
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People |
ORCID iD |
| Kathryn Lindsay Ball (Principal Investigator) |
Publications
Uhrik L
(2021)
Hydrogen deuterium exchange mass spectrometry identifies the dominant paratope in CD20 antigen binding to the NCD1.2 monoclonal antibody.
in The Biochemical journal
| Description | A consultation has taken place and a draft report has been sent from the consultants in the USA. They are currently working with us with respect to the next step on the FOF application procedure. |
| Exploitation Route | The findings from the consultants report will be incorporated into a Super FOF application. A grant incorporating the findings fro the Pathfinder report has been submitted to the BBSRC and is currently under consideration. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The findings have focused our research efforts on canine cancers f high unmet clinical need that would also provide economic benefit. |
| First Year Of Impact | 2018 |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | Optimizating the expression of a recombinant anti-CD20 IgG for the treatment of canine lymphoma |
| Amount | £15,500 (GBP) |
| Funding ID | BBSRC IAA PIII-024 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2018 |
| End | 07/2019 |
| Title | Canine CD20 specific antibody |
| Description | A comparative canine-human therapeutics model is being developed in B-cell lymphoma through the generation of a hybridoma cell that produces a murine monoclonal antibody specific for canine CD20. The hybridoma cell produces two light chains, light chain-3, and light chain-7. However, the contribution of either light chain to the authentic full-length hybridoma derived IgG is undefined. Mass spectrometry was used to identify only one of the two light chains, light chain-7, as predominating in the full-length IgG. Gene synthesis created a recombinant murine-canine chimeric monoclonal antibody expressing light chain-7 that reconstituted the IgG binding to CD20. Using light chain-7 as a reference sequence, hydrogen deuterium exchange mass spectrometry was used to identify the dominant CDR region implicated in CD20 antigen binding. Early in the deuteration reaction, the CD20 antigen suppressed deuteration at CDR3 (VH). In later time points, deuterium suppression occurred at CDR2 (VH) and CDR2 (VL), with the maintenance of the CDR3 (VH) interaction. These data suggest that CDR3 (VH) functions as the dominant antigen docking motif and that antibody aggregation is induced at later time points after antigen binding. These approaches define a methodology for fine mapping of CDR contacts using nested enzymatic reactions and hydrogen deuterium exchange mass spectrometry. These data support the further development of an engineered, synthetic canine-murine monoclonal antibody, focused on CDR3 (VH), for use as a canine lymphoma therapeutic that mimics the human-murine chimeric anti-CD20 antibody Rituximab. |
| Type Of Material | Antibody |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Publication |
| Description | HX-MS of CD20 antibody binding |
| Organisation | Masaryk Memorial Cancer Institute (MMCI) |
| Department | Regional Centre for applied Molecular Oncology |
| Country | Czech Republic |
| Sector | Hospitals |
| PI Contribution | We made the antibody |
| Collaborator Contribution | They carried out HX-MS |
| Impact | A publication in the Biochemical Journal |
| Start Year | 2019 |