In vivo dendritic cell reprogramming for cancer immunotherapy

被引：11

作者：

Ascic, Ervin ^{[1
,2
]}

Akerstrom, Fritiof ^{[3
]}

Sreekumar Nair, Malavika ^{[1
,2
]}

Rosa, Andre ^{[3
]}

Kurochkin, Ilia ^{[1
,2
]}

Zimmermannova, Olga ^{[1
,2
]}

Catena, Xavier ^{[1
,2
,3
]}

Rotankova, Nadezhda ^{[4
]}

Veser, Charlotte ^{[4
]}

Rudnik, Michal ^{[4
]}

Ballocci, Tommaso ^{[1
,2
]}

Schaerer, Tiffany ^{[3
]}

Huang, Xiaoli ^{[3
]}

de Rosa Torres, Maria ^{[1
,2
]}

Renaud, Emilie ^{[3
]}

Velasco Santiago, Marta ^{[5
]}

Met, Ozcan ^{[5
,6
]}

Askmyr, David ^{[7
,8
]}

Lindstedt, Malin ^{[9
]}

Greiff, Lennart ^{[7
,8
]}

Ligeon, Laure-Anne ^{[4
]}

Agarkova, Irina ^{[4
]}

Svane, Inge Marie ^{[5
]}

Pires, Cristiana F. ^{[3
]}

Rosa, Fabio F. ^{[3
]}

Pereira, Carlos-Filipe ^{[1
,2
,3
,10
]}

机构：

[1] Lund Univ, Lund Stem Cell Ctr, Mol Med & Gene Therapy, S-22184 Lund, Sweden

[2] Lund Univ, Wallenberg Ctr Mol Med, S-22184 Lund, Sweden

[3] Medicon Village, Asgard Therapeut AB, S-22381 Lund, Sweden

[4] InSphero AG, CH-8952 Schlieren, Switzerland

[5] Copenhagen Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, DK-2730 Herlev, Denmark

[6] Tech Univ Denmark, Dept Hlth Technol, DK-2800 Kongens Lyngby, Denmark

[7] Skane Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-22185 Lund, Sweden

[8] Lund Univ, Dept Clin Sci, S-22184 Lund, Sweden

[9] Lund Univ, Dept Immunotechnol, Medicon Village, S-22381 Lund, Sweden

[10] Univ Coimbra, Ctr Neurosci & Cell Biol, Largo Marques Pombal, P-3004517 Coimbra, Portugal

来源：

SCIENCE | 2024年 / 386卷 / 6719期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

FUNCTIONAL-NEURONS; RESPONSES; ANTIGEN; FIBROBLASTS; CDC1;

D O I：

10.1126/science.adn9083

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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