Fig. 1.

Mechanisms responsible for loss of target antigen, conferring resistance to CAR T cell therapy. A Due to tumor heterogeneity before any treatment, pre-existing antigen-negative tumor cells may be responsible for resistance to CAR T cell therapy. B Point mutations or altered alternative splicing may lead to a truncated target antigen that can no longer be recognized by CAR T cells. C Defect in target antigen maturation and trafficking due to lack of appropriate chaperon proteins may be responsible for target antigen membrane expression loss. D Exceptionally, a tumor cell may be transfected with the CAR vector leading to an epitope masking by the CAR itself and hiding the target antigen from the CAR T cells. E Lineage switch may be responsible for a complete phenotypic markers remodeling including loss of the target antigen