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February 2, 2026Journal of NanobiotechnologyOpen Access

CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes delivering C646 reverse CD8⁺ T Cell exhaustion via H3K18la histone delactylation in gastric cardia adenocarcinoma

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Authors

ZXZheng XiangThe Second Affiliated Hospital of Bengbu Medical CollegeXZXinxin ZhangJiading District Central HospitalYWYe WangXinjiang Agricultural University

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Overview

This research demonstrates a novel nanotechnology approach reversing T cell exhaustion in gastric cancer, suggesting enhanced immunotherapy potential.

Key Points

  • The aim is to investigate a method to reverse the exhaustion of CD8+ T cells in gastric cardia adenocarcinoma using biomimetic ectosomes.
  • Developed CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes encapsulating C646.
  • Conducted single-cell RNA sequencing on human GCA tissues to analyze epigenetic changes.
  • Investigated the effects of C646 on histone modifications and T cell function in vitro.
  • Tested CD8a-NVEs@C646 in a humanized orthotopic GCA model.
  • C646 reduced H3K18 lactylation and improved CD8+ T cell function by suppressing PDCD1 expression.
  • CD8a-NVEs@C646 demonstrated superior targeting, biocompatibility, and T cell proliferative capacity.
  • In vivo, CD8a-NVEs@C646 significantly inhibited tumor growth, enhancing T cell infiltration and apoptosis when combined with anti-PD-1 therapy.

Cite This Study

Xiang et al. (2026) studied this question.

synapsesocial.com/papers/6980fd81c1c9540dea80f3dfhttps://doi.org/10.1186/s12951-025-03957-z
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