RESEARCHERS OF IMMUNE-IMAGE REPORTED ABOUT THEIR RECENT SCIENTIFIC FINDINGS DURING EMIM IN SALZBURG
On 14-17 March the 18th European Molecular Imaging Meeting (EMIM) took place in the heart of Salzburg, the city of Mozart. The focus was on quantification in molecular imaging, cellular imaging, x-ray/lung imaging, neuroimaging, and hyperpolarized MRI. Researchers of the Immune-Image project gave 2 oral presentations in the parallel sessions and presented 3 posters in dedicated poster walks. In this article we share the summaries of their presentations and posters.
Summary of presentation of Timo de Groof
Timo gave a presentation about his study which focuses on developing human CD8β-targeting nanobody-based immunotracers for non-invasive nuclear imaging of CD8+ T cells during anti-cancer immunotherapy.
The presence and activity profile of tumor-infiltrating immune cells may predict responsiveness to (immuno)therapy. More specifically, CD8+ cytotoxic T cells are believed to be the main effector cells during anti-cancer responses. Therefore, non-invasive imaging of these cells is believed to be able to predict and/or follow up immunotherapy efficacy in cancer patients.
Timo explains: ”In this study, we have developed novel human CD8β-targeting nanobody-based immunotracers for non-invasive nuclear imaging of CD8+ T cells during anti-cancer immunotherapy. Our results show that our novel CD8β-targeting nanobodies bind recombinant CD8β protein and (primary) CD8+ T cells with high affinity. Moreover, the CD8β-targeting nanobodies bind more specifically to primary CD8+ T cells compared to CD8α-targeting nanobodies, which also target other immune cells. Upon radiolabeling, the CD8β-targeting nanobodies are able to visualize human CD8+ T.
Overall, these immunotracers could be interesting tools to allow same-day imaging to predict and/or follow up immunotherapy responses in patients with cancer and other CD8+ T cell driven pathologies.”
Summary of poster presentation of Yoline Lauwers
In her poster at the EMIM2023, Yoline presented her research focussing on the development of a nanobody-based immunotracer to non-invasively image the CD163 receptor, which is expressed on immunosuppressive tumor-associated macrophages (TAMs).
She explains: ”Non-invasive imaging of different immune cells inside the tumor microenvironment could predict the patients’ response to immunotherapy. In this study, we want to investigate the presence and prognostic value of immunosuppressive tumor-associated macrophages (TAMs) during anti-cancer immunotherapies. We have developed a nanobody-based immunotracer to non-invasively image the CD163 receptor, a receptor expressed on this immunosuppressive subset of macrophages. The cross-reactive lead anti-CD163 nanobody that was generated shows good binding towards the recombinant human and model CD163 receptor and HEK293T m-hCD163+ cells. Furthermore, the radiolabeled CD163-targeting immunotracer is able to specifically visualize CD163+ macrophages in naïve and LLC-OVA tumor bearing model.”
To conclude, when the predictive value of CD163-expressing macrophages is established, the radiolabeled nanobody-based immunotracer could be a promising clinical imaging agent to predict immunotherapy response in cancer or other disorders such as inflammation and thereby contribute to personalized medicine.
The work presented is linked to that work package of the IMI2JU Immune-Image project aiming for the generation of imaging reagents.
Summary of presentation of Jessica Wijngaarden
Jessica gave a presentation about her study on the use of 89Zr-immuno-PET for measuring target engagement of immune checkpoint inhibitors in several healthy organs. The work is linked to one of the tasks of the IMI2JU Immune-Image project, which aims to implement tracer pharmacokinetic models to understand the kinetic behavior of 89Zr-mAbs.
Jessica explains: ‘’Positron emission tomography with zirconium-89 labeled monoclonal antibodies (89Zr-immuno-PET) allows assessing whole-body mAb biodistribution. The measured PET uptake, however, consists of target specific uptake and non-target specific uptake (due to e.g. catabolism of mAbs). In this study, we show target engagement of immune checkpoint inhibitors in several healthy organs by means of two different approaches:
(1) comparing the uptake with previously established values for non-specific uptake, and
(2) by observing target saturation with increasing mass doses.
The two approaches in this study use Patlak linearization. This study improves our understanding of the kinetic behavior of 89Zr-mAbs in healthy tissue and uses 89Zr-immuno-PET to measure target engagement.’’
Summary of poster presentation of Julia Baguña Torres
During her poster presentation at EMIM2023, Julia Baguña Torres talked about the evaluation of a 89Zr-labeled anti-CD4 minibody in models of acute and chronic ulcerative colitis. She explained that the radiotracer produced high-contrast images of lymphoid organs by 24h post-injection and showed higher accumulation in the distal colon and rectum compared to healthy controls, particularly in the chronic colitis model. Furthermore, the models with chronic colitis showed significantly higher tracer concentration in the mesenteric lymph nodes and reduced splenic 89Zr-anti-CD4 uptake than their wildtype counterparts.
Overall, 89Zr-df-IAB46 was able to detect the presence of CD4+ T-cells in the models showing signs of acute and chronic DSS-induced colitis and holds promise as a tool to investigate CD4+ T-cell infiltration in preclinical models of inflammatory bowel disease and improve clinical management of UC patients as well as drug optimization.