Asgard Therapeutics announces publication on direct reprogramming of cancer cells to force antigen presentation, in collaboration with Lund University
- The research article entitled “Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming” was published today in Science Immunology. The study was led by Asgard’s co-founder Filipe Pereira in collaboration with Asgard Therapeutics and other international partners.
- The research demonstrates the ability of Asgard’s technology to reprogram cancer cells into professional antigen-presenting cells, suppressing tumorigenesis and inducing in-vivo anti-tumor immunity in models resistant to checkpoint inhibitors.
- These findings support Asgard’s lead cancer immunotherapy program AT-108 which is progressing to advanced pre-clinical development, with an IND planned for 2026.
Lund, Sweden – July 7, 2023 – 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 represents a significant milestone for Asgard’s reprogramming technologies, providing the foundation for the ongoing development of its in-vivo engineering programs.
To access the publication: DOI: 10.1126/sciimmunol.add4817
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 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.
The illustration depicts a novel Trojan horse approach to cancer immunotherapy by reprogramming cancer cells to become traitors to their kind. Using the minimal regulatory network of type 1 conventional dendritic cells (connections and cells inside the horse), Zimmermannova & Ferreira et al. reprogrammed human and mouse cancer cells into dendritic cells. This strategy bypassed tumor evasion mechanisms and endowed tumor cells with professional antigen presentation leading to activation of specific CD8+ T cells (soldiers), and anti-tumor immunity in vivo. This study paves the way for a new class of cancer immunotherapies based on cell fate reprogramming. Credit: Sandeep Menon.
For investor relations:
Cristiana Pires, Co-founder, and CEO
+46 (0) 731 566 072
For scientific inquiries:
Fábio Rosa, Co-founder, and Head of Research
+46 (0) 763 059 937
Filipe Pereira, Professor and Group leader at Lund University
+46 (0) 72 243 00 14
About Asgard Therapeutics®
Asgard Therapeutics is a private biotech company exploring the application of direct cell reprogramming technologies for cancer immunotherapies. Formed as a spin-off from Lund University, the Company is pioneering a gene therapy approach based on its proprietary reprogramming technology, designed to set in motion immune responses based on the biological properties of professional antigen-presenting cells. Backed by Novo Holdings, Boehringer Ingelheim Venture Fund, and Industrifonden, Asgard Therapeutics aims to build a pipeline of personalized cancer immunotherapies optimized for each unique patient. For more information, please visit: www.asgardthx.com.
About the Pereira Lab at Lund University
Professor Filipe Pereira is head of the Cell Reprogramming in Hematopoiesis and Immunity Group at the Lund University Stem Cell Center (LSCC). LSCC is one of six Swedish strategic centers of excellence in life sciences. Filipe Pereira is considered an influential researcher in the cell reprogramming field with >45 publications, >3,300 citations. Find more at https://pereiralab.com/ and https://www.stemcellcenter.lu.se/.