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New CAR T Strategy Targets Tumor Macrophages, Triggers Antitumor Immunity in Mice

Researchers report durable tumor regressions in multiple mouse models using an antigen‑independent, macrophage‑targeted approach.

Overview

  • A Cancer Cell study from Mount Sinai and Washington University describes IL‑12–armored CAR T cells designed to recognize and deplete tumor‑associated macrophages and reprogram the tumor microenvironment.
  • Treatment in metastatic lung, ovarian, and pancreatic mouse models extended survival with many complete cures reported.
  • Initial macrophage‑targeting CAR T protocols paired with lymphodepletion caused systemic toxicity, which was mitigated by lower‑dose IL‑12 delivery without lymphodepletion.
  • Spatial transcriptomics revealed removal of immunosuppressive cells and recruitment of cytotoxic CD8 T cells and proinflammatory myeloid cells within tumors.
  • The team stresses the work remains preclinical and is refining control of IL‑12 release to improve safety before any human testing.