On April 11, 2023 InSphero, a Swiss SME, reported, together with the REPRINT project partners, Asgard Therapeutics (SE, project coordinator), Lund University (SE) and Antineo (FR), the achievement of proof-of-principle for using dendritic cell reprogramming to kick start in-vivo anti-tumor immunity (Press release, Asgard Therapeutics, APR 11, 2023, https://www.asgardthx.com/eurostars-funded-reprint-consortium-reaches-milestones-with-evidence-of-complete-tumor-regression-induced-by-dendritic-cell-reprogramming/ [SID1234629932]). This joint successful milestone comes as the biggest output of the second in-person meeting hosted by InSphero and held last week in Zurich.
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The REPRINT (REPRogramming tumor INTo Immune Cells: a revolutionary gene therapy to treat cancer) project is a research initiative funded by the EUROSTARS program with the aim to develop an innovative off-the-shelf cancer immunotherapy based on Asgard Therapeutics’ proprietary in-vivo reprogramming technology. During these 1,5 years of activities, the four partners have provided extensive proof-of-principle for reprogramming tumor cells into antigen-presenting dendritic cells as a way to restore tumor immunogenicity, using both ex-vivo 3D and in-vivo models. Remarkably, reprogrammed cancer cells have the ability to activate local and systemic polyclonal tumor-specific immune responses, leading to complete tumor regression in animal models.
Cristiana Pires, PhD, Co-Founder and CEO of Asgard Therapeutics, said: "Since its launch in October 2021, the REPRINT project has made remarkable progress towards the development of a new cancer immunotherapy based in in-vivo reprogramming of tumor cells. We are thrilled with the recent in-vivo results, which showed that reprogramming can cure tumor-bearing animals! In addition, Asgard has selected the final platform to enable efficient delivery of the reprogramming factors to tumors in-situ and provided extensive validation of reprogramming from a multitude of human patient-derived tumor cells, which supports the platform potential of our lead program. There’re also exciting results coming supporting the ultimate vision for our lead program. During our recent in-person meeting, we had the opportunity to delve over the progress made and align priorities for future work with our consortium partners. It has been an absolute pleasure to collaborate with such an outstanding team to accelerate the development of our pioneering reprogramming therapies."
Wolfgang Moritz, Head of Ext. Collaborations and IP at InSphero AG said: "The consortium meeting in Zurich was a great success. We are honored to be a part of this historic project and we are excited to work with such a talented group of experts in the field. We are reporting the achievement of two major milestones at this meeting. First, we efficiently replicated tumor cell reprogramming into dendritic cells in our ex-vivo 3D Microtissue Platform. Using high content confocal imaging, we were able to visualize emerging dendritic cells and assess the efficiency of viral transfection and reprogramming. Second, we have successfully tested the prototype of a new plate. The AKURA TWIN plate accommodates the tumor models, together with liver or pancreatic islet microtissues, both in coculture with immune cells in adjacent wells, connected by a small channel. This breakthrough will enable the simultaneous evaluation of on- and off-target effects of tumor-dendritic cell reprogramming. InSphero’s proprietary in vitro technology will validate clinical benefits of a new therapeutic approach and de-risk potential safety concerns."
Filipe Pereira, PhD, Professor and Group leader at Lund University commented: "At this consortium meeting in Zurich, we were excited to discuss progress and define objectives with the entire REPRINT team for the cDC1 reprogramming approach created in our lab. We are grateful to join forces with this great team to pave the way for an entirely new cancer immunotherapy platform based on cellular reprogramming. At this meeting, we discussed the in-vivo results which showed that tumor-bearing models can be cured by our reprogramming strategy! This is a milestone providing proof-of-principle for a new cancer immunotherapy based on in-vivo reprogramming of tumor cells. We also showed that reprogramming progressed in human spheroid models with or without the presence of an immunosuppressive component of the tumor microenvironment. We are looking forward for development of the second half of this exciting project."
Marie Tautou, PhD, Study Director of Antineo added: "In the context of this consortium, we are thrilled to announce great progress in the establishment of 3D bioprinted cancer cells cubes that have allowed us to show efficient in vitro reprogramming of cancer cells into dendritic cells. In parallel, we have started experiments aiming to show the ability of Asgard’s gene therapy to reprogram tumor cells in vivo and we have exciting promising results. We are now focusing on the project’s next steps, which are to show the innocuity of the strategy in mice models. We are very pleased to be part of such a ground-breaking project."
The Eurostars programme supports innovative international projects led by R&D-performing SMEs and is co-funded by the Eurostars partner states and the EU (through Horizon 2020). In October 2021, Asgard Therapeutics announced that together with the other three partners it has been awarded the Eurostars project REPRINT (project number E!115376). The three-year proposal was ranked #4 out of 644 European applications for Eurostars Cut off 15 and thereby secured a grant of 2 million euros.