LY9 expression

Conclusion These data highlight the pre-treatment features of both tumor and T-cell that can pre-dispose real-world patients with RRMM to early relapse after anti-BCMA CAR-T, notably pre-existing T-cell exhaustion, and the presence of highly proliferative plasma cells with underlying resistance mechanisms, including downregulation of several known immunotherapy targets, especially in those with co-existing EMD. Ciara L Freeman, Xiaohong Zhao & Mark B Meads contributed equally

We identified a CD229 CAR binding domain with micromolar affinity that, when combined with overexpression of c-Jun, confers antitumor activity comparable to parental CD229 CAR T cells but lacks the parental cells' cytotoxic activity toward healthy lymphocytes in vitro and in vivo. The results represent a promising strategy to improve the efficacy and safety of CAR T cell therapy that requires clinical validation.

The described methodology is simple and allows the objective identification of residual populations in a single tube, no need to merge files or calculate data for the analysis. All the selected markers are necessary to maximize the discriminative potential of the technique. Larger studies are required in order to find out if the increase in CD28 expression or the appearance of different subclones in the residual populations may be related to chemoresistance and clonal selection phenomena.

At our institution, we have developed an academic BCMA-BBζ CART product (ARI2h; NCT04309981) for relapsed/refractory MM patients with encouraging results... This is the first bispecific BCMA/CD229 CART cell that adequately controls BCMA-expressing and non-expressing myeloma cells. This approach could mitigate disease escape due to biallelic loss of BCMA.

Additionally, we developed a co-culture method combined with the immunofluorescence assay to confirm that intercellular tyrosine phosphorylation mediated self-activation of CD229 to activate RAS/ERK signaling pathway via interacting with RASAL3. Taken together, these findings not only demonstrate the oncogenic role of CD229 in MM cell proliferation, but also illustrate the potential of CD229 as a promising therapeutic target for MM treatment.

CD229 can be used for the identification of PC and due to relatively homogenous expression; it can be used as a suitable marker for targeted therapies. However, precise discrimination of NPC from APC cannot be reliably achieved with CD229, limiting its utility as a useful marker of diagnostic relevance and MRD assessment in MM.

This study shows that CD229 can be used for the identification of PCs and due to relatively homogenous expression; it can be used as a suitable marker for targeted therapies. However, CD229 is not a satisfactory marker for discriminating NPC from APC, thus limiting its ability as a useful marker of diagnostic relevance and residual disease assessment in MM cases.

This study shows that CD229 can be used for the identifi cation of PCs and due to relatively homogenous expression; it can be used as a suitable marker for targeted therapies. However, CD229 is not a satisfactory marker for discriminating NPC from APC, thus limiting its ability as a useful marker of diagnostic relevance and residual disease assessment in MM cases.

In conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.

Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target.

Using a novel unbiased mutagenesis approach, we show that generation of minimally altered low affinity variants from existing antibodies is feasible and results in binders with substantially reduced affinity. Low affinity variants show increased selectivity eliminating a key liability of CD229 CAR T cells.

Finally, CD229 CAR T cells are effective against primary CLL cells from patients that have relapsed from CD19 CAR T cell therapy and do no exhibit antigen loss by trogocytosis. Taken together, these data suggest that CD229 CAR T cell therapy may be a promising option to address the poor outcomes for patients with relapsed B cell lymphoma.