The Modular CAR: Adapting T Cells without Reengineering Them

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Cancer Immunol Res. 2026 Sep 4:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0906. Online ahead of print.

ABSTRACT

The therapeutic potential of chimeric antigen receptor (CAR) T cells has long been limited by the static nature of the engineered receptor; once manufactured, the cell is committed to a single antigen, unable to respond to the immune evasion and antigen heterogeneity that define solid tumors. Although solutions such as bispecific constructs and logic-gated circuits have been proposed, each encodes additional complexity into the cell product at the time of manufacture, with no capacity for post-infusion reprogramming. In this issue, Kuo and colleagues report a fundamentally different strategy-the meditope-enabled CAR-in which a small, structurally orthogonal peptide-docking interface is embedded into the extracellular domain of the CAR, converting a fixed cellular product into a programmable platform that can be redirected, selectively expanded, or precisely tracked by administering a modular adapter molecule. See related article by Kuo et al., p. XX.

PMID:42695598 | DOI:10.1158/2326-6066.CIR-26-0906

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