Counteracting antigen loss
Tumor cells may become resistant to the CAR T cells by losing the epitope that is recognized by the CARs. Such antigen-escape tumor variants limit the efficacy of CAR-based therapies. In the case of CD19-directed CARs, this is called ‘CD19 negative escape’. Approximately 20-30% of patients relapse after CD19-directed CAR T cell therapy as a result of CD19 negative escape.
Scientists are developing approaches to prevent antigen negative escape, as was discussed by many speakers. Dual targeting is a common approach. For instance, scientists at UCL are developing novel CAR T cells that target both CD19 and CD22 (presented by Claire Roddie). This is also frequently done in China. Combining CAR T cell therapy with other substances may also be used to counteract target loss; the meeting featured several examples of this approach (see 'Combinatorial therapy').
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