Multiple Myeloma Treatment through Targeted Treg Depletion

In a landmark study Dr. Julia Dahlhoff published in the journal Leukemia  a groundbreaking approach to combat multiple myeloma (MM). The paper from our team, titled “Transient Regulatory T-Cell Targeting Triggers Immune Control of Multiple Myeloma and Prevents Disease Progression,” uncovers the potential of briefly depleting regulatory T-cells (Tregs) to unleash the body’s own immune system to eradicate this challenging blood cancer.Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression. Julia Dahlhoff, PhD, Andreas Beilhack Lab, Würzburg University Hospital, Germany, Europe, Immunotherapy program targeting regulatory T cells

Multiple myeloma, characterized by the proliferation of malignant plasma cells in the bone marrow, often relapses due to the protective niche created by bone marrow-resident Tregs. The study reveals that Tregs not only cluster around malignant plasma cells but also support their survival and dissemination.

Using two syngeneic immunocompetent murine models, the team under the leadership of Prof. Andreas Beilhack demonstrated that temporary depletion of Tregs in mice with established MM led to a robust immune response, mediated by CD8 T cells and natural killer (NK) cells, resulting in complete and sustained remission of the disease.

“Targeting Tregs disrupts their suppressive grip on the immune system, allowing CD8 T cells and NK cells to attack and eliminate myeloma cells,” said Dr. Dahlhoff. “This short-term intervention effectively prevented MM progression and offers a new therapeutic strategy that minimizes the risk of autoimmunity.”

The study paves the way for developing Treg-targeted therapies, providing a novel avenue for treatment-resistant multiple myeloma.

Reference: 

Dahlhoff J, Manz H, Steinfatt T, Delgado-Tascon J, Seebacher E, Schneider T, Wilnit A, Mokhtari Z, Tabares P, Böckle D, Rasche L, Martin Kortüm K, Lutz MB, Einsele H, Brandl A, Beilhack A. (2022). Transient regulatory T cell targeting triggers immune control of multiple myeloma and prevents disease progression. Leukemia 36(3):790-800.