Skip to main content

Immune-Image: Specific Imaging of Immune Cell Dynamics Using Novel Tracer Strategies

Periodic Reporting for period 2 - Immune-Image (Immune-Image: Specific Imaging of Immune Cell Dynamics Using Novel Tracer Strategies)

Reporting period: 2020-10-01 to 2021-09-30

Immune-Image aims to develop new imaging technologies to study the effects of modern immune therapies in cancer and inflammation patients (Fig. A), which are very successful but unfortunately only in a subset of patients. Our research should lead to new technologies where we can use Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and Optical Imaging (OI) to assess if an immune therapy is successful for an individual patient and, even better, to predict if an immune therapy will be effective. If we understand why patients do not respond to immune therapy, we could also design new drugs that will benefit these patients. Imaging is optimally suited for this purpose because a highly sensitive, whole body signal will be measured and the results will be complementary to cellular biology measurements on biopsies.
22 partner institutions work closely together to achieve this overall objective. The work program is divided in 5 scientific and 2 supportive work packages (Fig. B).
WP1 has created the organizational structure to optimally execute the scientific work program, has established a process to disseminate the project results including social media and takes care of informing patients about immunotherapies in general and the goals of Immune-Image in particular by means of a brochure as well as a video animation in 10 EU languages. In order to advance the development of a long-term strategy for the sustainability of the project results, a sustainability and knowledge transfer team was formed.

WP2 identified the data management needs from the research institutes involved in the various clinical (WP6) and pre-clinical (WP4) trials and offered centrally organised solutions to harmonize data collection, processing, sharing, and analysis. The collected information regarding multi-centre data management will be used to update the data management plan. The accreditation programs for clinical PET(/CT) image acquisition set up in period I have been implemented in several imaging centres involved in WP6. Harmonization of pre-clinical PET imaging has been initiated through implementation of centrally organised phantom experiments in collaboration with WP4. A legal overview report highlighting applicable regulations and high-level templates for SOPs and procedures has been shared within the consortium.

WP3 The in vitro and first in vivo characterization of lead human CD8β-targeting, human CD69-targeting and CD163-targeting nanobodies has been performed/ is ongoing. The generation of the bispecific CD8β/CD69-targeting nanobody has been initiated. The S100A9-targeting small molecules and nanobodies are currently being characterized in vitro and in vivo. The workflow to generate PD-1 and PD-L1-targeting peptides has been established. Protocols to label immune cells with a long-lived PET isotope for longitudinal cell tracking are being fine-tuned. The GMP-grade fluorescent labelled PD-L1 antibody is almost ready to be transferred to WP6 for clinical use.

WP4 focused on the establishment of imaging protocols for available immunotracers. In addition, models for in vivo cross validation were also successfully improved and progress was made towards establishing imaging protocols for the already available immunotracers in in the by WP4 successfully established murine IMID and tumor models.

WP 5investigated the impact of immune therapeutic interventions in various disease models in a longitudinal manner with already existing immune tracers and multi-modal imaging technologies.
The results so far validate the use of the immunotracers to assess the dynamics of immune cells in cancer and IMIDs, and therefore establish a solid basis of the proposed imaging platform.

The combined results of WP4 and 5 so far demonstrate the initial building of the proposed imaging platform to allow in vivo imaging of immunomodulatory therapies in cancer and IMIDs.

WP6 drafted or already submitted the clinical trial protocols and worked extensively on making the sites ready for execution of the clinical studies across sites. Moreover, the trial in rheumatoid arthritis is already ongoing.

WP7 continued to assess the relevant ethics requirement for research activities at all partners.
It is too early within the project to report about actual results of the project that have societal / economic impact. The overall progress beyond the state of art will be:

Impact on advancing the field of immune cell imaging
1. Immune-Image will deliver a systematic immunotracer generation platform and ensure that the platform endures beyond Immune-Image.
2. Ready-to-use set of validated PET and OI tracers will be produced. Additionally, MRI approaches to assess immunotherapy will be developed.
3. Immune-Image will produce regulatory accepted standardised protocols with validated immune-imaging approaches.

Advancing clinical and healthcare practice, improving European citizens' health and wellbeing, and making these sustainable
Immune-Image will provide insights into the immunological status of individual patients, which will lead to prediction of response to therapeutic interventions and provide insights into individual therapy responses. The patient will benefit with optimised therapies, increased safety and prevention of unnecessary side effects.

Boost & optimise drug discovery
The immunotracers resulting from Immune-Image will find immediate application in clinical trials, especially phase I and II. There, the immunotracers will be used to visualise and quantify the impact of immunotherapy on specific targets and immunological pathways, thereby reducing ambiguity in the evaluation of immunotherapy efficacy. This will lead to a reduction in the duration and costs of drug development and attract clinical research of pharmaceutical companies with new immune therapies in Europe.

Impact on basic & translational research
We envision Immune-Image will generate a number of academic demonstration studies, which will lead to opportunities for the development of novel therapeutic interventions. The results of Immune-Image will enable and facilitate R&D activities relevant to other diseases that have an immunological component. Finally, within Immune-Image new scientists in the field will be trained, who will drive future research.

Strengthening competitiveness and industrial leadership and addressing specific societal challenges
1. The immunotracer development platform will be used for addressing additional immune system-driven healthcare challenges. This will result in the creation of new jobs and attract additional private investments.
2. Immune-Image will facilitate trans-disciplinary and trans-sectoral collaboration and will boost the development of appropriate business models and generate the desired economic and employment impact at a global level.
3. Support European industrial leadership to successfully compete in the immunotherapy market worldwide .
4. We will actively reach out to European SMEs that focus on immunotherapy drug development to involve them within Immune-Image.
5. Support economic growth of industry by reducing unnecessary costs. For example, visualisation and quantification of the impact of therapy on specific sites and pathways is expected to decrease ambiguity in the evaluation of treatment efficacy in early stage clinical trials.
6. Increase awareness of the benefits that molecular imaging with immunotracers can create for patients and for all EU citizens.
Figure B: Overview on interactions between all work packages within Immune-Image.
Figure A: Scheme of the sustainable and flexible Immune-Image platform.