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April 5, 2026Cancer Research0 citations

Next-Generation CAR-T Cells Targeting Tumor Stroma with Enhanced Anti-Tumor Efficacy

Abstract 5195: Next-generation CAR-T cells that target only tumor stroma and matrix: Collagen-binding IL-12-expressing FAP-CAR-T show strong anti-tumor efficacy but are safe

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Authors

JIJ. IshiharaThe London CollegeCCChiu Po ChaunThe London CollegeKSKoichi SasakiThe London College

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Overview

Novel CAR-T therapy targets fibroblast activation protein to improve immune activation in solid tumors, suggesting a new therapeutic strategy.

Key Points

  • This study aims to develop a CAR-T therapy targeting cancer-associated fibroblasts to enhance anti-tumor efficacy and safety in fibrotic tumors.
  • Developed a novel CAR-T therapy targeting fibroblast activation protein (FAP).
  • Engineered CAR-T cells to express collagen-binding domain-fused interleukin-12 (CBD-IL-12).
  • Evaluated in vitro cytotoxicity against fibroblast cell lines and in vivo efficacy in murine models of breast and pancreatic cancers.
  • Conducted immunophenotyping to analyze immune cell infiltration in tumor microenvironment.
  • CBD-IL-12 expressing FAP CAR-T cells showed significant cytotoxicity against fibroblast cell lines in vitro.
  • In vivo, these CAR-T cells significantly suppressed tumor progression in breast and pancreatic cancer models.
  • CBD-IL-12 fusion led to over tenfold accumulation of IL-12 in tumor tissues while minimizing systemic toxicity.
  • Increased infiltration of CD8+ cytotoxic T lymphocytes and reduced regulatory T cells (Tregs) in treated tumors.

Cite This Study

Ishihara et al. (2026) studied this question.

synapsesocial.com/papers/69d1fca7a79560c99a0a2503https://doi.org/10.1158/1538-7445.am2026-5195
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Also Consider

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

  1. 1Abstract 1521: Concurrent targeting of tumors and their microenvironment using CAR-T cells specific for fibroblast activation protein alpha2026
  2. 2Efficacy and safety evaluation of cross-reactive Fibroblast activation protein scFv-based CAR-T cells2024 · 11 citations
  3. 3Antibody-mediated CAR T Platform for Targeting Tumor Cells and the Tumor Microenvironment 23016972026
  4. 4Dual-modular-nanobody CAR-T cell technical platform against the solid tumor microenvironment2026
  5. 5The Evolution of FAP-Targeted CAR T-Cell Therapy in Solid Tumors: From Immunotherapy to Immunotheranostic Applications2026