In vivo dendritic cell reprogramming for cancer immunotherapy-Reference-Cited by-同舟云学术

In vivo dendritic cell reprogramming for cancer immunotherapy

Published:2024-09-05 Issue: Volume: Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Ascic Ervin¹²^ORCID,Åkerström Fritiof³^ORCID,Sreekumar Nair Malavika¹²^ORCID,Rosa André³^ORCID,Kurochkin Ilia¹²^ORCID,Zimmermannova Olga¹²^ORCID,Catena Xavier¹²³^ORCID,Rotankova Nadezhda⁴,Veser Charlotte⁴^ORCID,Rudnik Michal⁴^ORCID,Ballocci Tommaso¹²^ORCID,Schärer Tiffany³^ORCID,Huang Xiaoli³^ORCID,de Rosa Torres Maria¹²^ORCID,Renaud Emilie³^ORCID,Velasco Santiago Marta⁵^ORCID,Met Özcan⁵⁶^ORCID,Askmyr David⁷⁸^ORCID,Lindstedt Malin⁹^ORCID,Greiff Lennart⁷⁸^ORCID,Ligeon Laure-Anne⁴,Agarkova Irina⁴^ORCID,Svane Inge Marie⁵^ORCID,Pires Cristiana F.³^ORCID,Rosa Fábio F.³^ORCID,Pereira Carlos-Filipe¹²³¹⁰^ORCID

Affiliation:

1. Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden.

2. Wallenberg Center for Molecular Medicine at Lund University, 221 84 Lund, Sweden.

3. Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden.

4. InSphero AG, 8952 Schlieren, Switzerland.

5. National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, 2730 Herlev, Denmark.

6. Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.

7. Department of ORL, Head & Neck Surgery, Skåne University Hospital, 221 85 Lund, Sweden.

8. Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden.

9. Department of Immunotechnology, Lund University, Medicon Village, 223 81 Lund, Sweden.

10. Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adn9083

Reference58 articles.

1. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy

2. Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy

3. CD4 ⁺ T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses

4. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

5. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study