202A cancer immunotherapy modality based on dendritic cell reprogramming in vivo

Filipe Pereira, Ervin Ascic, Fritiof Åkerström, Malavika Sreekumar Nair, André Rosa, Ilia Kurochkin, Olga Zimmermannova, Xavier Catena, Nadezhda Rotankova, Charlotte Veser, Michal Rudnik, Tommaso Ballocci, Tiffany Schärer, Xiaoli Huang, Emilie Renaud, Marta Velasco Santiago, Özcan Met, David Askmyr, Malin Lindstedt, Lennart GreiffIrina Agarkova, Inge Marie Svane, Cristiana Pires, Fábio Rosa

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Immunotherapy leads to long-term survival of 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 complete tumor regressions, and established long-term systemic immunity in different 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 first-in-human trials and other applications of immune cell reprogramming in vivo..
Original languageEnglish
Article number2026
JournalExperimental Hematology
Volume137
Issue numberSuppl.
Pages (from-to)104584
Number of pages1
ISSN0301-472X
DOIs
Publication statusPublished - 2024

Fingerprint

Dive into the research topics of '202A cancer immunotherapy modality based on dendritic cell reprogramming in vivo'. Together they form a unique fingerprint.

Cite this