# Antigen escape (antigen loss, lineage switch)

Source: https://onco.cc/terms/antigen-escape/  
OnCo record `antigen-escape` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell
- Wikipedia: https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell

## Connected records

- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Flow cytometry (immunophenotyping)](https://onco.cc/terms/flow-cytometry/), [T-cell exhaustion and CAR-T persistence](https://onco.cc/terms/t-cell-exhaustion-term/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Logic-gated therapeutics (AND, NOT gates)](https://onco.cc/technologies/logic-gated-therapeutics/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [BCMA](https://onco.cc/targets/bcma/), [CD19](https://onco.cc/targets/cd19/)
- biomarkers: [BCMA expression](https://onco.cc/biomarkers/bcma-expression/), [CD19 expression (CD19-positive)](https://onco.cc/biomarkers/cd19-expression/), [CD20 expression (CD20-positive)](https://onco.cc/biomarkers/cd20-expression/), [CD22 expression (CD22-positive)](https://onco.cc/biomarkers/cd22-expression/), [GPRC5D expression](https://onco.cc/biomarkers/gprc5d-expression/)

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