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August 1, 2026Journal of Hematology & OncologyOpen Access

A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection

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Authors

ÁRÁngel Ramírez-FernándezABAdham S. BearEKElahe Kamali

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Overview

Randomized trial demonstrates enhanced tumor control in mixed HLA contexts, suggesting improved therapeutic strategies.

Key Points

  • The aim is to develop a platform that combines KRAS targeting with mRNA engager redirection in γδ T cells.
  • Engineered primary human γδ T cells with KRASG12V/HLA-A*11:01 TCR.
  • Lipid nanoparticle (LNP) delivered mRNA encoding bispecific T cell engager (M5).
  • Evaluated anti-tumor effects in humanized mouse models with varying KRAS and HLA expressions.
  • γδ A11v T cells effectively lysed KRASG12V/HLA-A*11:01 positive tumor cells in vitro and in vivo.
  • LNP-M5 enhanced γδ A11v T cell counts and redirected T cells to kill mesothelin positive targets.
  • Combining γδ A11v T cells with LNP-M5 resulted in complete responses and prolonged survival in mixed tumor models.

Cite This Study

Ramírez-Fernández et al. (2026) studied this question.

synapsesocial.com/papers/6a6d9868e258b358b3c6bbdahttps://doi.org/10.1186/s13045-026-01836-0
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