📢 Exciting News! Asgard Therapeutics, in collaboration with the Pereira lab, is happy to announce the publication of a preprint in bioRxiv called “A cancer immunotherapy modality based on dendritic cell reprogramming in vivo” showcasing in vivo proof-of-concept for our lead program AT-108, a replication-deficient adenoviral vector encoding our proprietary combination of dendritic cell-inducing transcription factors. The study supports the ability of AT-108 to: • Transduce and reprogram tumor cells to conventional type 1 dendritic cells in vivo. • Remodel the tumor microenvironment and promote recruitment and expansion of polyclonal cytotoxic T cells. • Induce complete tumor regression in checkpoint blockade-resistant models. • Establish long-term systemic immunity. This research represents a significant milestone for Asgard Therapeutics' lead program, AT-108, which is currently in the preclinical development stage and expected to reach IND-readiness by 2026. We extend our gratitude to all co-authors for their great contributions to this groundbreaking research. Read the full pre-print paper on bioRxiv: bit.ly/463KeKY
Professor at Lund University, Wallenberg Fellow in Molecular Medicine, Co-founder of Asgard Therapeutics and Editor-in-Chief of Cellular Reprogramming
I am proud to release the pre-print of our proof-of-concept in situ reprogramming strategy, titled: “A cancer immunotherapy modality based on dendritic cell reprogramming in vivo”. In Ascic et al., we reprogram tumor cells in situ to efficiently present antigens as type 1 conventional dendritic cells (cDC1s). We have previously reprogrammed cancer cells to a cDC1-like cellular fate in vitro by expressing three transcription factors PU.1, IRF8 and BATF3 (collectively termed PIB). The tumor microenvironment (TME) often creates an immune suppressive phenotype. This results in insufficient antigen presentation and explains the low success rate of current immunotherapeutic strategies. We asked if we could induce cDC1 reprogramming within the TME. We followed a sequential strategy: in vivo reprogramming of syngeneic mouse models; reprogramming of human spheroids and xenograft models; and optimization of intratumoral reprogramming factor delivery. Reprogramming reshaped the TME, elicited T cell expansion and remarkable tumor remissions. Interestingly, we showed that the 3D environment favors acquisition of cDC1 fate and function. We further compared delivery systems and assessed the dose-dependency of this potential therapy. When expressing PIB with adenoviruses within tumors in mice, we observed that reprogrammed cDC1-like cells establish systemic and durable anti-tumor immunity. This in situ approach sets the stage to first-in-human evaluation of this new modality of cancer immunotherapy. This study was directed by the amazing PhD student Ervin Ascic together with Malavika Sreekumar Nair, Ilia Kurochkin at the Lund Stem Cell Center WCMM LU WCMM LU and in close collaboration Asgard Therapeutics and other great partners at Lund University and around the world. Let us know what you think of our findings. If you are at the #ISSCR2024, come talk face-to-face!