Fig. 1.

An immunotherapeutic approach for targeting LOH. A schema describing the proposed cellular engineering strategy to target LOH events in cancer. Arrows labeled “Allele A” and “Allele B” depict the production of a polymorphic protein as a result of transcription and translation of a polymorphic gene subject to LOH in cancer. The NASCAR platform comprises pairwise CAR and iCAR receptors in T cells. Concurrent engagement of both receptors will result in iCAR-mediated quenching of proximal CAR signaling and divert T cell activation away from normal cells expressing both alleles (Left). However, cancer cells that have undergone LOH will trigger the CAR but not the iCAR, resulting in NASCAR T cell activation (Right).