Depletion of Host CD122⁺ Cells Facilitates Widespread Skeletal Multiple Myeloma Engraftment in NOD/SCID Recipients

To facilitate human multiple myeloma (MM) engraftment into NOD/SCID recipients, mice were depleted of CD122⁺ cells (NK and myeloid cells) by antibody-mediated ablation prior to transplantation with the MM cell lines (RPMI8226, RPMI8226-TGL or U226). The MM engraftment, skeletal MM distribution, osteolysis, lambda chain paraprotein and associating disease symptoms in CD122⁺ cell-depleted and CD122⁺ cellreplete mice were compared. The CD122⁺ cell-depleted mice engrafted at a significantly higher frequency with human CD38⁺, CD56⁺, PCA-1⁺ and CD138⁺ cells. In the CD122⁺ cell-depleted mice, bioluminescence MM signal involved the whole mouse compared to limited imaging signal in the CD122⁺ cell-replete mice. The majority 88%–100% of CD122⁺ cell-depleted mice developed MM engraftment throughout the appendicular and axial skeletons with osteolysis and rare subcutaneous plasmacytomas (11% of mice). Serum paraprotein appeared earlier at 4–5 weeks post-transplant in CD122⁺ cell-depleted mice and continued to increase during the 12–13 weeks of analysis. The majority, 92% of CD122⁺ cell-depleted mice developed hind-limb paralysis and had a significantly shortened 45 day survival. Thus, depletion of CD122⁺ cells reduced resistance to the human MM and produced a new MM xenograft-NOD/SCID model that recapitulates the clinical manifestations of MM and eliminates the major limitations associated with the published MM xenograft-mouse model.