CRISPR/Cas9-mediated PD-1 attenuation enhances tumor infiltrating lymphocyte-based adoptive cellular therapy in humanized-PDX model of hepatocellular carcinoma.

ABSTRACT:

Background

Tumor-infiltrating lymphocyte (TIL)-based adoptive cellular therapy (ACT) has become a promising therapeutic approach due to its ability to effectively control disease in multiple types of solid tumor. Antibodies against the negative immune checkpoint programmed cell death protein 1 (PD-1) have been widely used in cancer immunotherapy. We hypothesized that PD-1 depletion in hepatocellular carcinoma (HCC) TIL-derived T cells would enhance their anti-tumor efficacy.

Methods

CRISPR/ Cas9 system was employed to target PDCD1 in HCC TIL-derived T cells. The phenotypic and functional changes were analyzed by flow cytometry. T-cell receptor (TCR) sequencing and bulk RNA-sequencing of PD-1-edited or non-edited T cells was conducted to examine their differences. Finally, we

SUBMITTER: Ge W 

PROVIDER: S-EPMC12399210 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature