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

Informations projet

Immune-Image

N° de convention de subvention: 831514

DOI

10.3030/831514

Date de signature de la CE 26 Septembre 2019

Date de début 1 Octobre 2019

Date de fin 31 Mars 2027

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 27 154 551,37

Contribution de l’UE

€ 15 000 000,00

Coordonné par

STICHTING AMSTERDAM UMC
Netherlands

Periodic Reporting for period 5 - Immune-Image (Immune-Image: Specific Imaging of Immune Cell Dynamics Using Novel Tracer Strategies)

Période du rapport: 2023-10-01 au 2024-09-30

Résumé du contexte et des objectifs généraux du projet

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 PET, MR and 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 because a highly sensitive, whole-body signal will be measured, and the results will be complementary to cellular biology measurements on biopsies (Fig. B).

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Communication activities towards public and patients were continued. By promoting sustainable thinking through workshops and discussions the consortium is being guided towards sustainability either of individual achievements or the organizational and technological structure.
We centrally organised solutions to harmonize data collection, processing, sharing, and analysis. Information for multi-centre data management to design a data management plan was collected. Solutions were developed and implemented to enable future clinical data capture, exchange of images, and findability of biosample meta-data. The accreditation programs for clinical image acquisition with PET were implemented in several imaging centres. Harmonization of pre-clinical PET imaging was implemented and a legal report highlighting applicable regulations and high-level templates shared within the consortium. A prototype of analytical methods for semi-automatic quantification of tracer intensity/volume in PET was developed.
The in vitro and first in vivo characterizations of several new nanobody tracers targeting CD8β, CD69, S100A9 and CD163 are progressing as expected. Generation of the bispecific CD8β/CD69-targeting nanobody has now resulted in some compounds showing promising results but remains a challenging task. We also developed S100A9-targeting small molecules which are being optimized and characterized. Works towards new peptides and nanobodies targeting PD-1 and PD-L1 resulted in the first promising hits which a will be tested in vivo shortly. We have established a new methodology to label immune cells and a GMP-grade fluorescent labelled PD-L1 antibody was transferred to clinical use.
Precise imaging standardized protocols have been established, while models for in vivo cross validation were further improved with, amongst others, an experimental vasculitis model and humanized mouse models. Consequently, the several immunotracers were successfully transferred to advanced preclinical study for longitudinal assessment of immune cell tracking as well as monitoring of different treatment approaches.
The impact of therapeutic interventions in various disease models in a longitudinal manner was investigated with several immunotracers and multi-modal imaging technologies. The results indicate the high value of immunotracers to assess the dynamics of immune cells in various disease model systems in vivo and underline the value of the proposed imaging platform.
Most of the exploratory clinical trials with our immunotracers have been initiated and a recruiting patients, one of the studies is already finished and the results have been published recently in a high standing scientific journal. Two clinical trials are in final preparation to open for inclusion of volunteers. Finally, the last clinical study where we will do a first in human study with one of the newly developed PET immunotracers within our project is in final stages of preparation and we aim to include first volunteers end of 2025.

Publications:
[1] Wijngaarden et al. https://zenodo.org/records/10870381
[2] De Groof et al. https://zenodo.org/records/13693441
[3] Pezzana et al. https://zenodo.org/records/13220307
[4] Gabriëls et al. https://zenodo.org/records/10949987

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The overall progress beyond the state of art will be:
Impact on advancing the field of immune cell imaging
1. The project will deliver a systematic immunotracer generation platform. To ensure that the platform endures beyond Immune-Image, we are about to spin-out a service providing company.
2. Ready-to-use set of validated PET and OI tracers will be produced. Additionally, MRI approaches to assess immunotherapy will be developed. Several patent applications were submitted to secure future sustainable use of the results of Immune-Image.
3. Immune-Image has produced regulatory acceptable 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. First results are published with our new optical imaging tracer in a high ranked journal [4].
Boost & optimise drug discovery
Immunotracers resulting from Immune-Image have found application in clinical trials. First results are published, the other studies are still on-going. There, the immunotracers are 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 the EU.
Impact on basic & translational research
Immune-Image generated the first academic demonstration study, and several more will follow which will lead to opportunities for the development of novel therapeutic interventions. The project results will enable and facilitate R&D activities relevant to other diseases that have an immunological component. Finally, within Immune-Image new scientists will be trained who will drive future research in the field.
Strengthening competitiveness and industrial leadership and addressing specific societal challenges
1. The immunotracer development platform has been 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 has facilitated trans-disciplinary and trans-sectoral collaboration, which 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, e.g. 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 A: Scheme of the sustainable and flexible Immune-Image platform.