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December 10, 2025Science Translational Medicine

ZAP327 signaling domain–driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse models

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Authors

XLXin LiuJZJiayi ZhangJCJunjun Chu

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Overview

Preclinical findings show ZAP327 CAR T cell therapy improves immune response and reduces exhaustion in blood cancers, suggesting new approaches for solid tumors.

Key Points

  • To evaluate the effectiveness of ZAP327-driven chimeric antigen receptor (CAR) T cells in combating blood cancers and solid tumors.
  • Construction of CARs with ZAP70-derived signaling domain (ZAP327)
  • Assessment of T cell persistence and antitumor activity in mouse models
  • Comparative analysis of cytokine release and T cell exhaustion markers
  • Evaluation of costimulatory domains like CD28 and 4-1BB
  • ZAP327-driven CAR T cells showed enhanced therapeutic antitumor activity compared to conventional CAR T cells
  • Reduced cytokine release and expression of T cell exhaustion markers observed
  • Increased persistence and pools of stem-like memory T cells were noted
  • Mechanistically associated with improved metabolic features via oxidative phosphorylation

Cite This Study

Liu et al. (2025) studied this question.

synapsesocial.com/papers/69401d542d562116f28f88e8https://doi.org/10.1126/scitranslmed.adz0529
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Also Consider

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

  1. 1ZAP327 signaling domain–driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse models2025
  2. 2Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs2024 · 3 citations
  3. 3Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screening and single-cell sequencing2024 · 2 citations
  4. 4Reprogramming CAR with cytokine signaling increases the efficacy of CAR-T cell therapy in solid tumour treatment and confers sustained immune memory2026 · 1 citations
  5. 5In vivo screening of TCR-based chimeric antigen receptors for improved anti-tumor functionality2025