See article, p. 146.
CAR T cell (CART) therapy elicits clinical response in the majority of patients with multiple myeloma, but is often followed by a relapse. Loss of the CAR-targeted antigen expression by cancer cells is common at relapse and is considered among the main mechanisms limiting durability of response. Here Fernández de Larrea and colleagues develop approaches for simultaneously targeting BCMA and GPRC5D myeloma antigens by a single CART infusion. They demonstrate that BCMA/GPRC5D dual-specific CARTs eliminate myeloma cells positive for both antigens and protect mice from rechallenge with BCMA-negative myeloma cells. CART performance was best when BCMA/GPRC5D was introduced as a single bicistronic vector, as compared to pooled CARTs individually transduced with BCMA and GPRC5D, and with a vector encoding a bivalent CAR. If reproduced with other CARs, these findings suggest that bicistronic vectors are an optimal strategy to dual CART manufacture. It remains to be...
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