Authors:

Erin Trachet and Maryland Rosenfeld Franklin

Year:

2017

AACR Hematologic Malignancies Conference

“Preclinical Models of Multiple Myeloma”

Introduction and Background

  • Multiple myeloma is a clonal B cell malignancy characterized by the accumulation of terminally differentiated, antibody-producing plasma cells in the bone marrow that is invasive and drug resistant. Patients are generally asymptomatic until very late state disease. There are few preclinical models that recapitulate human disease. In this work, we have evaluated the human MM.1S model and the murine 5TGM1 model.
    • MM.1S was derived from a 42 year old African American woman and has been documented to express CD25, CD38, CD52 and CD59. It also expresses the glucocorticoid receptor and is dexamethasone sensitive.
    • 5TGM1 is a syngeneic model generated from the C57BL/KaLwRij mouse which is predisposed to develop several monoclonal B-cell proliferative disorders.

Results & Conclusions

  • MM.1S(pMMP-LucNeo) Human
    • Aggressive and reliable growth seen in both SCID Beige mice and NSG mice. In the more immune-deficient NSG mouse disease progresses more quickly with about 30 days to 50% survival vs. ~45 days in the SCID beige mouse.
    • Expression of CD138 is a hallmark of plasma cells and multiple myeloma cells. In a NSG study we determined, by flow cytometry, that >85% of the CD45- gate in the bone marrow was CD138+ on study day 21 suggesting significant engraftment of the tumor cells within the bone marrow.
    • The optimization of MM.1S in NSG mice makes it an appealing model for novel CAR-T, TCR, and other cell-based therapies.
  • 5TGM1-luc Murine
    • Aggressive and reliable growth in both the syngeneic C57/KaLwRij strain and the immune-deficient NIH III (bg/nd/xid) mouse strains. Disease progression behaves similarly in both strains of mice, with significant tumor cells localizing in the spine and the long bones.
    • This model is suitable for testing immunotherapies and other classes of drugs.