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October 9, 2025Open Access

TCR activation impairs CAR-T cytotoxicity against separate target cells

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Authors

CMCarolin MoosmannFDFelix DrostNKNikolaj Pagh Kristensen

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Overview

Observational analysis reveals that TCR signaling impairs CAR-T cytotoxicity against separate antigens, suggesting a need for improved therapeutic strategies.

Key Points

  • TCR signaling reduces CAR-T cell cytotoxicity when targeting different antigens.
  • Anti-CD19 CAR-T clonotypes tracked in patients with B cell malignancies showed varied persistence.
  • Combination of CAR transduction and TCR replacement demonstrated altered cellular behavior.
  • Spatial separation of TCR and CAR antigens influences their interaction and therapeutic design.

Cite This Study

Moosmann et al. (2025) studied this question.

synapsesocial.com/papers/68e70db790569dd607ee67cahttps://doi.org/10.1101/2025.10.07.680634
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Also Consider

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

  1. 1The TCR in CAR T cell therapy: use it or lose it?2026
  2. 2Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation2025 · 7 citations
  3. 3CAR T cell cytotoxic responses are rapidly generated and sensitive to the unligated TCR2025
  4. 4Cytotoxic bystander activation of endogenous CAR-negative T cells in response to CD19-CAR T cell therapy 38362025
  5. 5CD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses2025 · 2 citations