TY - JOUR
T1 - 202A cancer immunotherapy modality based on dendritic cell reprogramming in vivo
AU - Pereira, Filipe
AU - Ascic, Ervin
AU - Åkerström, Fritiof
AU - Nair, Malavika Sreekumar
AU - Rosa, André
AU - Kurochkin, Ilia
AU - Zimmermannova, Olga
AU - Catena, Xavier
AU - Rotankova, Nadezhda
AU - Veser, Charlotte
AU - Rudnik, Michal
AU - Ballocci, Tommaso
AU - Schärer, Tiffany
AU - Huang, Xiaoli
AU - Renaud, Emilie
AU - Santiago, Marta Velasco
AU - Met, Özcan
AU - Askmyr, David
AU - Lindstedt, Malin
AU - Greiff, Lennart
AU - Agarkova, Irina
AU - Svane, Inge Marie
AU - Pires, Cristiana
AU - Rosa, Fábio
PY - 2024
Y1 - 2024
N2 - 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..
AB - 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..
U2 - 10.1016/j.exphem.2024.104584
DO - 10.1016/j.exphem.2024.104584
M3 - Journal article
SN - 0301-472X
VL - 137
SP - 104584
JO - Experimental Hematology
JF - Experimental Hematology
IS - Suppl.
M1 - 2026
ER -