Interview Nick Devoogdt about the progress within his work package

We interviewed Nick Devoogdt, Professor at Vrije Universiteit Brussel (VUB) and work package leader within Immune-Image, about the recent progress within his work package and the key areas he and his team are concentrating on until the end of the project. He also shares this thoughts about how Immune-Image can further build on the results of the project.

The following overview highlights the tasks in work package 3, mixing completed goals with ongoing promising technologies and tasks yet to be finalized but likely to continue beyond Immune-Image.

Task 3.1: Identification of lead nanobodies targeting CD8β, CD69 & CD163

‘We have successfully developed good nanobodies for each of the specified targets, achieving our goal completely. We are now at the stage where we aim to publish our findings. A manuscript describing the generation and imaging potential in mouse models of an anti-CD8β nanobody PET tracer has recently been accepted for publication in the ‘European Journal of Nuclear Medicine and Molecular Imaging’, a top scientific journal in the field. Another manuscript describing the development and testing in mice of an anti-CD163 nanobody PET tracer is in revision in another top journal, hopefully to be published soon. We also deposited patents on both compounds. However, the CD69 target is still in the preliminary stages, and further characterization is needed before we can publish. Despite this, we have created a lead nanobody compound that works in mice, and which is now being converted into a PET tracer. Thus, Task 3.1 is fully completed, and we have met our deliverables.’

Task 3.2: Generation of bi-specific nanobodies targeting CD8β+/CD69+ activated cytotoxic T-lymphocytes

‘This task is actively ongoing. Several compounds have been developed that show interesting binding characteristics on cultured cells, which we are currently trying to validate in mice. An additional grant was secured from ‘Kom op tegen kanker,’ a Flemish non-profit anti-cancer organization, to further develop this study beyond the scope of Immune-Image.’

Task 3.3: Development of a PET tracer against S100A9

‘Two parallel projects, both under the supervision of researchers from the university of Münster, are in their final stages. One involves a small molecule compound, and the other, nanobodies against S100A9. Although the latter was originally not part of the program, this subtask was created and is now nearing completion, with work package 4 validating the efficacy of the nanobody tracer. Both a patent and a publication are planned to be submitted in the coming weeks.’

Task 3.4: Development of small peptide tracers for imaging PD-1 and PD-L1

‘The work of Melinda Badenhorst from the University of Amsterdam, involves peptide creation against the targets. She identified promising peptides that meet the required characteristics, thus providing significant output for Immune-Image. Although the final goal to image these targets in mice won’t be achieved by the end of September, a follow-up is planned. Besides the experimental part, a narrative publication review has been published on the research objectives.’

Task 3.5: Radiolabelling of subsets of immune cells for tracking In vivo

‘Various parameters were tested for labeling immune cells using a new technique involving radioactive conjugation. However, it was decided that the technique isn’t powerful enough for clinical testing within Immune-Image. While promising results were achieved, they are currently not yet publishable.’

Task 3.6: Nanobody labelling optimization for PET and OI

‘Several techniques have been used and applied in Brussels (VUB), Münster (University of Munster), and Amsterdam (VUMC) for nanobody labelling, employing a range of radiochemical techniques and isotopes. While not spectacular, these techniques are effective, and the deliverable has been met.’

Task 3.7: GMP production of a new tracer vehicle

‘This ongoing aspect of work package 3 involves a Tracer Selection Committee evaluating all newly created tracers. The CD163 nanobody PET tracer from task 3.1 was selected for clinical implementation and is now in GMP production. This production is currently going on in a brand new clean room in Brussels, with the production expected to be completed by the end of the year. The GMP-nanobody precursor will be sent to Amsterdam (VUMC) for further labelling and then shipped to UMCG in Groningen and VUMC in Amsterdam for clinical trials, which are still in the design phase and expected to start patient inclusion in 2025/2026.’

Task 3.8: GMP-compliant labelling of nanobodies, peptides, small molecules, minibodies, and antibodies

‘Numerous nanobodies have been labelled within work package 3 at different sites. Currently, the fluor-labelling of the anti-CD163 nanobody is being undertaken at VUMC within Immune-Image, promising a significant deliverable. Early in the project, fluorescent antibodies were linked to a fluorescent dye in Groningen under GMP conditions and this compounds is currently being used in a clinical study in patients.’

Key focus areas until project end

‘Our primary focus is currently on GMP productions. Significant progress is being made with the anti-PD-L1 peptides at VUMC. We aim to bring the CD8 tracer into the clinic, a development that will continue post-Immune-Image. I have applied for a Belgian grant for the GMP production and clinical testing of our CD8 tracer. Immune-Image scientists are part of our advisory board, ensuring ongoing follow-up and connection. The anti-CD69 and the bispecific tracer development continues with national funding for optimization.’
Future prospects for building on Immune-Image results
‘We plan to initiate a first-in-human study with the CD163 tracer within Immune-Image. In Brussels, we aim to test this tracer further in various pathologies beyond the current project’s scope, for which funding has been requested. The bi-specific tracer concept developed within Immune-Image appears highly promising in vitro and will be expanded to new tracers. The support from Immune-Image has been invaluable in establishing our clean room facility, with the CD163 GMP production being the first product. This foundational work paves the way for future developments and products thanks to Immune-Image.’