Enhanced Myeloma Therapy: CDR101's Promising Preclinical Performance

The abstract discusses the development and testing of a new therapy for relapsed or refractory multiple myeloma (RRMM). BCMAxCD3 targeting treatments have shown positive effects but resistance is a concern. A new approach using a trispecific molecule, CDR101, which targets CD3, BCMA, and PD-L1, was found to be more effective than current bispecific formats. CDR101 was tested against two MM cell lines and showed superior T cell-mediated cytotoxicity. It also outperformed the combination of bispecifics and a PD-L1 inhibitor.

In bone marrow samples from RRMM patients, CDR101 induced significant lysis of primary MM cells and increased T cell activation. In vivo studies using a human MM xenograft model showed that CDR101 led to complete tumor regression in the majority of mice with no relapse observed.

The study concludes that targeting BCMA and blocking PD-L1 simultaneously with CDR101 could offer a more effective treatment for myeloma than existing therapies. CDR101's selective inhibition of PD-L1 at the immune synapse could potentially reduce immune-related adverse events and enhance therapeutic efficacy, indicating a promising clinical potential for this treatment.