In vivo gene editing of T-cells in lymph nodes for enhanced cancer immunotherapy

Jin Qu, Yuan Wang, Chuxiao Xiong, Mingxue Wang, Xingdao He, Weibin Jia, Cheuk Yin Li, Tianlong Zhang, Zixun Wang, Wei Li, Becki Yi Kuang and Peng Shi ()
Additional contact information
Jin Qu: Kowloon
Yuan Wang: Kowloon
Chuxiao Xiong: Kowloon
Mingxue Wang: Kowloon
Xingdao He: Kowloon
Weibin Jia: Kowloon
Cheuk Yin Li: Kowloon
Tianlong Zhang: Clear Water Bay
Zixun Wang: Chinese Academy of Sciences
Wei Li: Wuhan University
Becki Yi Kuang: Kowloon
Peng Shi: Kowloon

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Immune checkpoint blockade (ICB) therapy, while promising for cancer treatment, faces challenges like unexpected side effects and limited objective responses. Here, we develop an in vivo gene-editing strategy for improving ICB cancer therapy in a lastingly effective manner. The approach uses a conductive hydrogel-based electroporation system to enable nucleofection of programmed cell death protein 1 (PD1) targeted CRISPR-Cas9 DNAs into T-cells directly within the lymph nodes, and subsequently produces PD1-deficient T-cells to combat tumor growth, metastasis and recurrence in different melanoma models in mice. Following in vivo gene editing, animals show enhanced cellular and humoral immune responses along with multi-fold increases of effector T-cells infiltration to the solid tumors, preventing tumor recurrence and prolonging their survival. These findings provide a proof-of-concept for direct in vivo T-cell engineering via localized gene-editing for enhanced cancer immunotherapy, and also unlock the possibilities of using this method to treat more complex human diseases.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54292-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54292-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54292-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().