In Vivo T-Cell Editing in Lymph Nodes Effectively Combats Tumours0

A new method for directly editing T-cells in lymph nodes using CRISPR-Cas9 aims to enhance immune checkpoint blockade (ICB) cancer therapies. The novel strategy avoids the complexities of ex vivo cell engineering by directly editing immune cells in vivo.

By: Gorm Palmgren - Nov. 26, 2024

Researchers at City University of Hong Kong developed the technique that creates T-cells lacking PD1, a key immune regulator. The intervention improves their efficacy against tumour growth, metastasis, and recurrence in mice models.

Central to the new technique is a hydrogel-based electroporation system (hydro-EP) integrated into a surgical forceps-like device that delivers CRISPR-Cas9 plasmids targeting the PD1 gene into lymph node T-cells. During a minor surgical procedure, the lymph node is located and gently sandwiched between the hydro-EP device’s electrodes, one of which contains the preloaded plasmid DNA (see Figure 1).

Figure 1. Schematic of in vivo gene-editing in lymph node for localised T-cell engineering therapy... — Figure 1. Schematic of in vivo gene-editing in lymph node for localised T-cell engineering therapy through the conductive hydrogel-based electroporation system (hydro-EP) to enable nucleofection of PD1-targeted CRISPR-Cas9 DNAs into T lymphocytes directly within lymph node tissues. See the original paper for the complete figure legend. Reproduced under the Creative Commons license from Figure 1 in Qu et al. (2024) Nature Communications, doi.org/10.1038/s41467-024-54292-0

Mice treated with this method showed significant immune responses, with increased infiltration of effector T-cells into tumours, reduced metastasis, and prolonged survival. The edited T-cells showed sustained activity and eliminated tumour recurrence post-surgery in melanoma models.

The approach is presented as minimally invasive and scalable, reducing costs and risks associated with traditional methods like viral vectors. This proof-of-concept study suggests a potential for broader applications in treating cancers and complex diseases through localised gene editing.

The study was led by Peng Shi at City University of Hong Kong and published yesterday in Nature Communications.

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