Anti-CD38 VLRB-Fc antibodies from transgenic tobacco exhibit potent anti-myeloma activity in vitro and in vivo.

Multiple myeloma (MM) is an incurable hematological malignancy characterized by the abnormal proliferation of malignant plasma cells. While current therapies, particularly anti-CD38 monoclonal antibodies such as daratumumab, have improved patient outcomes, they are often associated with high costs and potential adverse effects. Therefore, there is a growing need for alternative, cost-effective therapeutic strategies. In this study, we report for the first time the successful generation of a plant-derived lamprey variable lymphocyte receptor B (VLRB) recombinant antibody, targeting CD38-expressing MM cells. Two versions of the plant-derived antibodies were engineered by fusing a lamprey-derived anti-CD38 VLRB domain to a human IgG Fc region (Fc) and an ER-retention KDEL signal (K). The first version, anti-CD38 VLRB-stalk-FcK, contains a stalk domain, whereas the second version, anti-CD38 VLRB-FcK, does not. Both antibodies were subsequently expressed in transgenic tobacco plants. Following purification, their binding affinity, cytotoxic effects, and immune effector functions were assessed in vitro using CD38+ MM cell lines. Anti-CD38 VLRB-stalk-FcK demonstrated superior CD38 binding, cytotoxicity, ADCC and inhibition of cell migration compared to anti-CD38 VLRB-FcK. In vivo experiments demonstrated that treatment with anti-CD38 VLRB-stalk-FcK significantly inhibited tumor growth in NOD/SCID mice implanted with multiple myeloma (MM) xenografts. The anti-tumor effect observed was comparable to that achieved with daratumumab, a clinically approved anti-CD38 monoclonal antibody. These findings highlight a novel plant-based platform for producing lamprey-derived therapeutic antibodies, and support the potential of anti-CD38 VLRB-stalk-FcK as a cost-effective, alternative therapeutic agent for the treatment of multiple myeloma.