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November 25, 2025The Journal of ImmunologyOpen Access

Engineering Intracellular Signaling Domains to Drive CAR-T Cell Differentiation from Pluripotent Stem Cell 2865

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Authors

JYJiyoung YunMCMatthew ChanPZPeter W. Zandstra

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Overview

Engineering CAR T cells from induced pluripotent stem cells improves differentiation and reduces innate skewing in B cell lymphomas, suggesting new immunotherapy avenues.

Key Points

  • This research aims to improve differentiation of CAR T cells from induced pluripotent stem cells by engineering intracellular signaling domains.
  • Engineering CAR intracellular signaling domains to modulate tonic signaling.
  • Utilizing iPSC-derived CAR T cells for scalable therapy.
  • Conducting a CAR signaling domain library screen for optimal combinations.
  • Achieved a 2.5-fold reduction in tonic signaling index with a novel ICD combination.
  • Demonstrated a fivefold increase in CD4+CD8+ T cell precursors from engineered iPSCs.
  • Suggests enhanced differentiation away from innate-like phenotypes.

Cite This Study

Yun et al. (2025) studied this question.

synapsesocial.com/papers/692502be87af00ed34ac23e2https://doi.org/10.1093/jimmun/vkaf283.736
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Also Consider

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

  1. 1Abstract 39: Preclinical <i>in vitro</i> and <i>in vivo</i> evaluation of CD8αβ+ CD19 CAR iPSCs T cells generated in a TCR signal-independent manner using DLL4/VCAM-coupled microbeads2024
  2. 2Abstract 11: Development of innovative off-the-shelf cancer immunotherapies with iPSC-derived CD8-positive T-cells2024 · 1 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. 4Abstract A013: Programmable JAK/STAT signaling drives CAR T cells to enhanced functional states2026
  5. 5Identifying regulators of CAR-T cell survival and adaptation in the tumor microenvironment 36762025