Flow cytometry of a bone marrow sample from a patient with myeloma. (Right panel) Bone marrow contains a complex mixture of immune cells and blood cell progenitors that come in all shapes in sizes. (Left panel) Differentiating myeloma cells from this mixture requires the use of multiple cell surface markers with known expression patterns on these cells, such as CD38.
Naked antibodies attract components of the immune system, such as macrophages and natural killer (NK) cells to kill myeloma cells. Bispecific antibodies bind both myeloma and T-cells, activating the powerful killing activity of these cells. Antibody-drug conjugates are a targeted delivery system for highly potent chemotherapy directly into the myeloma cells.
Myeloma cells under the microscope, crowding out the normal bone marrow cells. Photo credit to Jessica Davis, MD.
Currently, there is no therapy capable of eliminating minimal residual disease (MRD) in myeloma, preventing cure, and inevitably leading to disease relapse in all patients. MRD contains cells that have disease regenerating capacity, behaving functionally as “myeloma stem cells” that eventually lead to relapse. It is our hope to develop a therapy approach capable of eliminating MRD, yielding curative potential for this disease. Towards this, we are implementing patient sample derived, MRD-focused strategies, including ex vivo assays of self-renewal activity and xenograft models for the testing of novel anti-myeloma therapeutics.