Remodeling of anti-tumor immunity with antibodies targeting a p53 mutant.

ABSTRACT:

Background

p53, the most frequently mutated gene in cancer, lacks effective targeted drugs.

Methods

We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess the function of mAbs in vitro and in vivo.

Results

These LNP-pE285K-mAbs in the IgG1 format exhibited a robust anti-tumor effect, facilitating the infiltration of immune cells, including CD8⁺ T, B, and NK cells. scRNA-seq revealed that IgG1 reduces immune inhibitory signaling, increases MHC signaling from B cells to CD8⁺ T cells,

SUBMITTER: Chai D 

PROVIDER: S-EPMC11184848 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature