Radio-Biological Enhancement of an Interleukin-6 Receptor Antibody by the β-Particle-Emitting Radionuclide Iodine-131 in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy defined by the accumulation of neoplastic plasma cells in the bone marrow. Although novel therapies have improved outcomes in patients with MM, most cases eventually relapse and become refractory, highlighting the need for new therapeutic strategies. Interleukin-6 (IL-6) plays a key role in MM progression by promoting tumor cell growth and survival. It promotes the growth of IL-6-dependent MM cells, and inhibition of IL-6 signaling could suppress their proliferation. However, the efficacy of the anti-IL-6 receptor antibody (Ab) tocilizumab (Toc) appears to be limited in IL-6-independent cases, and its clinical application has not yet been established. To enhance the therapeutic efficacy of Toc, an iodine-131 (131I)-labeled Toc was evaluated as a β-emitting radioimmunotherapy (RIT), which combines Ab specificity with the cytotoxicity of radionuclides to deliver targeted radiation to MM cells. In vitro assays demonstrated that the 131I-labeled Toc induced growth inhibition in both IL-6-responsive and IL-6-irresponsive MM cells. Furthermore, biodistribution studies and therapeutic evaluation in an MM xenograft mouse model revealed selective tumor accumulation and significant tumor growth suppression following intraperitoneal administration. These findings suggest that 131I labeling enhances the antitumor activity of Toc and may overcome the limitations of Toc monotherapy. Therefore, β-emitting RIT using 131I represents a promising strategy for MM, and further investigation into its mechanistic details is warranted.