In vivo dendritic cell reprogramming for cancer immunotherapy.

Autor: Ascic E; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Åkerström F; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Sreekumar Nair M; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Rosa A; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Kurochkin I; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Zimmermannova O; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Catena X; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden.; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Rotankova N; InSphero AG, 8952 Schlieren, Switzerland., Veser C; InSphero AG, 8952 Schlieren, Switzerland., Rudnik M; InSphero AG, 8952 Schlieren, Switzerland., Ballocci T; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Schärer T; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Huang X; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., de Rosa Torres M; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden., Renaud E; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Velasco Santiago M; Department of Oncology, National Center of Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, 2730 Herlev, Denmark., Met Ö; Department of Oncology, National Center of Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, 2730 Herlev, Denmark.; Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Askmyr D; Department of Otorhinolaryngology, Head & Neck Surgery, Skåne University Hospital, 221 85 Lund, Sweden.; Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Lindstedt M; Department of Immunotechnology, Lund University, Medicon Village, 223 81 Lund, Sweden., Greiff L; Department of Otorhinolaryngology, Head & Neck Surgery, Skåne University Hospital, 221 85 Lund, Sweden.; Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Ligeon LA; InSphero AG, 8952 Schlieren, Switzerland., Agarkova I; InSphero AG, 8952 Schlieren, Switzerland., Svane IM; Department of Oncology, National Center of Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, 2730 Herlev, Denmark., Pires CF; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Rosa FF; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Pereira CF; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.; Wallenberg Centre for Molecular Medicine at Lund University, 221 84 Lund, Sweden.; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden.; Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Oct 18; Vol. 386 (6719), pp. eadn9083. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1126/science.adn9083
Abstrakt: Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.
Databáze: MEDLINE
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