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19th International Myeloma Society Annual Meeting August 2022 S47 Abstracts Muhammad Kashif 1, Andreas Lundqvist 1, Hans-Gustaf Ljunggren 1, Hareth Nahi 2, Arnika Wagner 1, Evren Alici 1 1Karolinska Institute; 2Karolinska University Hospital Introduction: Multiple myeloma (MM) is a currently incurable hematological cancer. The expression of programmed death protein 1 (PD1) on immune cells and its ligand PD-L1 in the tumor microenvironment (TME) were shown in patients with MM. However, phase III clinical trials, looking into immune checkpoint inhibition with monoclonal antibodies (mAb) failed, emphasizing the need to optimize this approach. NK cell-based therapies are currently in early-phase clinical trials for MM, but NK cell dysfunctionality may occur via PD1-PD-L1 interaction. PD1-based chimeric switch receptors (CSR) were designed to revert NK cell inhibition upon PD1-PD-L1 interaction and …