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