Date: Thursday 22 June 2017
Time: 4 pm BST
Speakers: Dr Hidde Ploegh, Senior Investigator, Boston Children’s Hospital
Format: This will be an online presentation
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The ability to visualize immune responses non-invasively would have tremendous value for basic immunology. In pre-clinical models it would be possible to track events such as the host response to infections, to look at inflammation more generally, and to follow the course of interventions such as checkpoint blocking antibodies in the treatment of tumours.
PET imaging agents require a workflow compatible with the half-life of commonly used isotopes, and must take into account the pharmacokinetic properties of these agents. The specificity of what is being imaged requires the design of compounds that can distinguish between differences in metabolic activity (18F-fluorodeoxyglucose) or that serve as ligands for specific receptors, such as antibodies that recognize surface structures. We have used nanobodies, the smallest antibody-derived fragments that retain antigen-binding capacity. These fragments are ~15 kDa in size, are rapidly cleared from the circulation and are easily modified by chemo-enzymatic means for the installation of metal chelators or click handles to enable radiolabelling. Using nanobodies, we have been able to image various populations of immune cells, and based on longitudinal immuno-PET observations we have been able to make predictions of success and failure in immunotherapy of the B16 mouse melanoma model. The use of 89Zr-labelled nanobodies for immuno-PET will be a powerful adjunct to more conventional, invasive models, and will provide resolution superior to fluorescence- and luminescence-based models.
Dr Hidde Ploegh
Senior Investigator, Boston Children’s Hospital
Dr Ploegh received his PhD from Leiden University in the Netherlands. A contributor to over 500 papers, Dr Ploegh taught at Harvard Medical School, where he headed the school’s immunology program (1997–2005). Prior to that, Ploegh was a professor of biology at MIT, working in the Center for Cancer Research (now the David H Koch Institute for Integrative Cancer Research).
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