NK92 Expressing anti-BCMA CAR and Secreted TRAIL: a Promising Combination Treatment against Multiple Myeloma

• DOI: 10.20944/preprints202308.1611.v1
• Publication Date: 2023-08-24T00:35:06Z
• Authors: Benjamin Motais; Sandra Charvatova; Zuzana Walek; Roman Hajek; Juli Bagó
• Keywords: Viability assay

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation (BCMA), expressed widely on MM cells. To mitigate risks associated allogenic cells, we investigated the potential BCMA CAR expression natural killer (NKs), known for potent cytotoxicity minimal side effects. Using NK-92 line, co-expressed soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing PiggyBac transposon system. Engineered NK (CAR-NK-92-TRAIL) demonstrated robust against panel lines primary samples, outperforming unmodified mean difference viability 45,1% (± 26,1%, depending target line). Combination therapy was explored inhibitor bortezomib (BZ) γ-secretase inhibitors (GSI), leading significant synergistic effect combination CAR-NK-92-TRAIL This synergy evident assays where notable decrease observed combinatorial compared single treatment. In summary, our study demonstrate treatment MM. The impact combining these engineered BZ GSI supports further development CAR-based products effective therapy.