Despite the introduction of targeted immunotherapies, multiple myeloma is still a mostly incurable cancer. For a study, it was determined that limited expression on normal cells, together with high CS1 (SLAMF7) expression on myeloma cells, made it a promising CAR-T target. The CS1 protein contains two extracellular domains: the distal Variable (V) domain and the proximal Constant 2 (C2) domain.Luc90-CS1-CAR-T, a novel construct targeting the V domain of CS1, was developed and tested in the study. In vitro and in vivo anti-myeloma killing was observed in mice infected with two models. The researchers generated fratricide resistant CS1 deficient Luc90- CS1- CAR-T (ΔCS1- Luc90- CS1) after the CD8+ cells were destroyed during production. Ex vivo CAR-T cell cultures were then evaluated for safety and effectiveness, with no effect on the latter observed. In the case of myeloma, the data suggest that targeting the distal V domain of CS1 may have been an effective CAR-T therapy and clinical production did not produce any advantage when CS1 was deleted in vivo in immunodeficient NSG animal models.
Source:www.nature.com/articles/s41375-022-01559-4
