Asgard Therapeutics publicerar nya rön om direkt omprogrammering av cancerceller för att tvinga fram antigenpresentation

• Forskningsartikeln med titeln "Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming" har publicerats i Science Immunology. Studien leddes av Asgards medgrundare Filipe Pereira i samarbete med Asgard Therapeutics, Lunds universitet och andra internationella partners.
• Forskningen visar förmågan hos Asgards teknologi att omprogrammera cancerceller till professionella antigenpresenterande celler, undertrycka tumörbildning och inducera antitumörimmunitet in vivo i modeller som är resistenta mot checkpoint-inhibitorer.
• Dessa fynd stöder Asgards ledande cancerimmunterapiprogram AT-108 som går vidare till avancerad preklinisk utveckling, med en IND planerad till 2026.

-- -- -- -- --

Lund, Sweden – Asgard Therapeutics (“Asgard”), a private biotech company pioneering in-vivo direct reprogramming approaches for cancer immunotherapy, is proud to announce the publication in Science Immunology demonstrating reprogramming of over 60 mouse and human tumors cells across a broad spectrum of tumor types into functional antigen-presenting cells. This study[1] represents a significant milestone for Asgard’s reprogramming technologies, providing the foundation for the ongoing development of its in-vivo engineering programs.

 

Fabio Rosa, PhD, Co-Founder and Head of Research at Asgard Therapeutics, said: “This study represents a major output of our long-lasting collaboration with the Pereira Lab at Lund University focusing on the unique anti-tumor properties of conventional type 1 dendritic cells (cDC1s). We showed for the first time that reprogrammed cDC1s kick start in-vivo anti-tumor immunity, leading to complete regression of tumors! In addition, reprogramming induced loss of tumorigenic properties in cancer cells, supporting the feasibility of moving towards an in-vivo engineering approach. At Asgard, we have recently selected our lead candidate AT-108, an off-the-shelf gene delivery vector encoding our proprietary combination of reprogramming factors. AT-108 is delivered directly in-vivo to recreate cDC1s’ functional properties in tumor cells and kick-start personalized anti-tumor immunity, bypassing limitations of ex-vivo cell therapies and complex tumor neoantigen identification. AT-108 is now moving into advanced pre-clinical development with IND planned for 2026.”

 

Filipe Pereira, PhD, Co-founder and Head of Innovation at Asgard Therapeutics, Professor and Group leader at Lund University said: “Cancer cells downregulate antigen presentation to evade immune surveillance. Reversal of this mechanism has been attempted with definite mediators and downstream pathways, but we wanted to take it a step forward. By applying our knowledge of cell fate reprogramming, we have now demonstrated that the minimal transcription factor network of cDC1s[2] can be applied to engineer cancer cells’ identity. We observed that a common cDC1 and antigen presenting signature (of more than 600 genes) was commonly upregulated across mouse and human cancer cells, including patient-derived samples from 7 indications, broadly activating downstream pathways critical for efficient anti-tumor immunity (i.e. class I and II MHC molecules, co-stimulatory signaling, IL-12, CXCL10, among others). Our findings support the platform potential of our reprogramming approach which armed cancer cells with the ability to present their own endogenous tumor antigens and activate in-vivo cytotoxic CD8+ T cell responses, leading to increased survival of tumor-bearing mice”.

 

The study was led by Filipe Pereira in a collaborative effort between his team in the Cell Reprogramming in Hematopoiesis and Immunity Group at Lund University Stem Cell Center (LSCC), Asgard Therapeutics, a member of SmiLe Incubator, and its collaborators, Inge Marie Svane from the National Center of Cancer Immune Therapy in Denmark, Lennart Greiff and Malin Lindstedt from Lund University, among many others. The research at Asgard has been carried out with support from the Eurostars-2 Joint Program with co-funding from the European Union's Horizon 2020 research and innovation program, and Sweden's Innovation Agency, E!115376 REPRINT Grant 2021-03371, and the Strategic innovation programs Swelife and Medtech4Health, a joint venture by Vinnova, Formas and the Swedish Energy Agency, Grant 2020-04744.

---

---