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TIM‑3 Triplet Therapy Shows Promise in Immunotherapy‑Resistant Melanoma Models

Preclinical results support clinical testing focused on TIM‑3 in resistant melanoma.

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Identification of anti-TIM-3 based checkpoint inhibitor combinations with activity in immunotherapy refractory melanoma models

Overview

  • Moffitt Cancer Center researchers report that adding TIM‑3 blockade to PD‑1 and LAG‑3 restored anti‑tumor activity in laboratory and animal models that had resisted standard immunotherapy.
  • The regimen produced tumor shrinkage with complete regressions in some models, according to the Journal for ImmunoTherapy of Cancer paper published on Aug. 18, 2025.
  • Analysis of melanoma patient tumor samples showed higher TIM‑3 expression in non‑responders to prior immunotherapy, pointing to a potential second‑line target.
  • The triple‑drug combination did not show increased immunotoxicity in preclinical testing, though safety and efficacy in humans remain to be established.
  • Investigators led by Keiran Smalley indicate plans to move the strategy into clinical trials, with support from NIH, Florida’s Bankhead‑Coley program, and the Huntsman Cancer Foundation.