Title:
New technologies and capabilities supporting the development of novel Molecular RadioTherapy agents
Autors:
Sarah Belderbos1, Celine Mothes1, Claire Bernhard2, Franck Denat2, Pierre Adumeau1, Alexandra Garancher1, Agnieszka Kownacka1, Calmen Tihansky3, Marie Ruch2, Michael Claron2, Mathieu Moreau2, Cyril Berthet1, Eftychia Koumarianou1
1.Oncodesign Services, Dijon, France, 2. ICMUB Institut de Chimie Moléculaire de l’Université de Bourgogne, Dijon, France, 3. ImaginAb, Bracknell, UK
Abstract :
At Oncodesign-Services we aim to provide cutting-edge technologies and products to support the development of radiopharmaceuticals for theranostics.
Starting from the optimization of lead compounds, the site-specific bioconjugation chemistry of a bifunctional chelator to large biological compounds, such as antibodies, can preserve the biological profile and the reliable batch production. Thanks to new technologies we can conjugate a variety of payloads (cytotoxins, radioactive chelates, fluorescent dyes) on antibodies at targeted lysine residues of the Fc region, independent of Fc glycosylation.
Moreover, we aim to use relevant models for valuable translational results. In line with this, we established tumor spheroids to finely monitor the diffusion and subcellular distribution of novel fluorescent and radioactive probes in a 3D environment.
Furthermore, we are currently generating two animal tumor models for optimal target expression levels and recapitulation of the human tumor microenvironment. Our first model is a PSMA+ expressing tumour model, in a non radiosensitive rodent strain allowing improved assessment of novel radiopharmaceuticals. Our second tumor model is under development to assess novel FAPI tracers.
In parallel, we are developing a 89Zr/177Lu based theranostic pair, to harness both PET and SPECT-imaging capabilities of 89Zr and 177Lu simultaneously. Zirgonium-89 (89Zr, t1/2=3.3d) as PET imaging agent and Lutetium-177 (177Lu, t1/2=6.7d) as its therapeutic counterpart, present similar half-lives coinciding with the long biological half-life of large molecules, such as antibodies. Our focus has been to establish parameters for the dual 89Zr-PET and 177Lu-SPECT imaging coregistration, to monitor disease progression and map the uptake of therapeutic agents over time in tissues, organs and tumor lesions.
Finally, we present in partnership with ImaginAb 89Zr Crefmirlimab Berdoxam, a minibody (human and murine analog) with high affinity to the CD8α glycoprotein, a valuable PET imaging tool for preclinical tracking and assessment of CD8 cells. This PET imaging can be used to evaluate immunoresponse following treatment, autoimmune, inflammatory and/or infectious diseases models.
To conclude, our continuous efforts aim at expanding our service portfolio to fulfil the needs of our various projects, as presented herein. Our experience and expertise allow us to suggest alternatives based on the latest technological progresses to facilitate and expedite the drug discovery progress from bench to bedside.
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