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T-cell receptor gene therapy targeting KRAS G12V for advanced pancreatic cancer in a single-arm phase 1/2 clinical trial - PubMed

12 hours ago
  • #Pancreatic cancer
  • #T-cell therapy
  • #KRAS G12V
  • T-cell receptor gene therapy targeting KRAS G12V was tested in a phase 1/2 clinical trial for advanced pancreatic cancer.
  • Five patients with recurrent pancreatic cancer received autologous T cells engineered to target KRAS G12V.
  • Three patients received multiple infusions, with primary endpoints being safety and objective response rate.
  • Most common grade 3+ adverse event was hematologic toxicity due to lymphodepletion.
  • One patient achieved a complete response lasting 5.5 months, while two had short-term stable disease.
  • TCR-T cells were detected in peripheral blood of four patients one month post-first infusion.
  • No clinical responses were observed with TCR-T retreatment.
  • Hyper-acute rejection occurred in two patients after retreatment, likely due to persistent antibodies against the engineered TCR.
  • Study highlights safety, therapeutic potential, and challenges of repeat TCR-T infusions for KRAS G12V pancreatic cancer.