2026 – A CANCER IMMUNOTHERAPY MODALITY BASED ON DENDRITIC CELL REPROGRAMMING IN VIVO

IF 2.5 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2024-08-01 DOI:10.1016/j.exphem.2024.104584

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 Greiff , Fábio Rosa

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引用次数: 0

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.

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2026 - 基于树突状细胞体内重编程的癌症免疫疗法模式

免疫疗法可使癌症患者长期存活，但由于抗原呈递不足以及肿瘤微环境中免疫原性细胞的排斥，免疫疗法的普遍成功一直受到阻碍。在这里，我们开发了一种方法，通过腺病毒递送转录因子PU.1、IRF8和BATF3，在体内对肿瘤细胞进行重编程，使它们能像1型传统树突状细胞一样呈递抗原。重编程的肿瘤细胞重塑了肿瘤微环境，招募并扩增了多克隆细胞毒性T细胞，诱导肿瘤完全消退，并在不同的小鼠黑色素瘤模型中建立了长期的全身免疫力。在人类肿瘤球体和异种移植物中，重编程为免疫原性树突状细胞的过程不受免疫抑制的影响，而免疫抑制通常会限制免疫疗法。我们的研究为首次人体试验和体内免疫细胞重编程的其他应用铺平了道路。

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来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

期刊介绍： Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.