OnCo
termsTerm

Antigen escape (antigen loss, lineage switch)

aka antigen escape, antigen loss, antigen-negative relapse, CD19-negative relapse, CD19-negative, BCMA-negative, BCMA loss, target loss, target downregulation, antigen downregulation, antigen-low, lineage switch, lineage plasticity, trogocytosis, antigen heterogeneity, antigen-negative

When a cancer treated with a therapy aimed at one surface marker (CD19, BCMA, HER2) survives by shedding that marker, so the drug has nothing to grab. About a third of relapses after CD19 CAR-T are antigen-negative.

Mechanisms include mutations or splice variants that remove the epitope, deletion of the gene (TNFRSF17/BCMA biallelic loss in myeloma), lineage switch (B-ALL relapsing as myeloid leukaemia under CD19 pressure), trogocytosis (CAR-T cells stripping antigen off tumour cells), and pre-existing antigen-low subclones. Responses are dual-targeting CARs (CD19/CD22, BCMA/GPRC5D), sequencing to a different antigen (GPRC5D or FcRH5 after BCMA), logic-gated CARs and antigen-independent strategies. It is distinct from T-cell-intrinsic failure (exhaustion, poor persistence), which is the other main cause of relapse, and flow cytometry at relapse distinguishes the two.

Category
Treatment jargon

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