HETEROTRANSPLANTATION OF HUMAN MULTIPLE-MYELOMA CELL-LINES IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) MICE

Human multiple myeloma (MM) xenografts have been difficult to establis h in athymic mice. We examined the feasibility of establishing human M M xenograft growth in SCID mice following subcutaneus (sc) injection o f 1-2x10(7) cells from the human plasma cell dyscrasia (PCD) cell line s RPMI 8226 and ARH-77. SC tumors emerged in 67% (619) of RPMI 8226- a nd 6 of 6 ARH-77 - injected mice after a latency period of 9-54 days, and reached 19-35 mm in diameter before the mice were sacrificed. RPMI 8226 and ARH-77 primary tumor DNA hybridized positively with the huma n genome probe Alul-(Blur8), confirming successful engraftment of the human MM cell lines. The RPMI 8226 xenografts comprised predominantly of plasmacytoid cells that expressed the relevant cytoplasmic immunogl obulin (cIg) light chain isotype. Xenografted RPMI 8226 cells also exp ressed CD10 (CALLA; 44% reactive cells), CD38 (OKTIO; 69%), CD5 (49%), and reacted with the MM monoclonal antibody MM4 (39%). Human MM growt h appeared to be localized subcutaneously for both RPMI 8226 and ARH-7 7 xenografts. There were no detectable metastatic foci in kidney, brai n, heart, or bone marrow. Whereas diffuse plasma cell infiltrates were observed in spleen, GI tract, and lung biopsies of tumor-bearing mice , these infiltrates were of host origin according to immunophenotyping and DNA analyses. Neither the originating RPMI 8226 line nor its SCID mouse xenograft expressed Epstein Barr virus (EBV) genome sequences. These observations indicate that both EBV- (RPMI 8226) and EBV+ (ARH-7 7) cell lines can be successfully propagated in SCID mice. These xenog rafts retained the antigenic features of human MM, and may be useful f or assessing immunotherapeutic approaches for this disease.