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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 XiangXZXinxin ZhangYWYe Wang

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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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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Reprogramming CD8+ T-cell branched N-glycosylation limits exhaustion, enhancing cytotoxicity and tumor killing2025
  2. 2Abstract LB293: Cystine restriction enhances CD8+ CAR-T potency by promoting OXPHOS via GCN2-eIF2α-SLC1A5 axis2026
  3. 3CD8⁺ T cell membrane-camouflaged cerium oxide nanozyme enables targeted delivery of a Gsk3β inhibitor to the immunological synapse, reconstructing immunological synapse homeostasis and alleviating limited immunotherapeutic responses in solid tumors by decoupling the β-Catenin-TIPE-PD-1 enhancer complex2026
  4. 4NK Cell‐Derived Small Extracellular Vesicles Armed With CLDN4‐Targeting Peptides Potentiate Radiotherapy in Gastric Cancer2025
  5. 5Data from Reprogramming CD8<sup>+</sup> T-cell Branched <i>N-</i>Glycosylation Limits Exhaustion, Enhancing Cytotoxicity and Tumor Killing2025