A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect

Abstract

BackgroundThe development and preclinical testing of novel immunotherapy strategies for multiple myeloma can benefit substantially from a humanized animal model that enables quantitative realtime monitoring of tumor progression. Here we have explored the feasibility of establishing such a model in immunodeficient RAG2

Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors

“…To examine whether these characteristics translated into anti-tumor efficacy in vivo, we evaluated daratumumab in two mouse xenograft tumor models, based on Daudi lymphoma and UM-9 multiple myeloma cells stably expressing the luciferase gene (19,20).…”

“…For the mouse UM9 tumor xenograft model, experiments were performed essentially as decribed by Rozemuller et al (20). Briefly, 20 3 10 6 UM9-luc cells were injected i.v.…”

“…Daudi-luc cells and UM-9-luc cells were generated as described previously (19)(20)(21). Ramos cells were provided by Prof. J. Golab (Department of Immunology, Center of Biostructure Research, The Medical University of Warsaw, Warsaw, Poland).…”

Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

“…Daudi cells were transfected with gWIZ luciferase as previously described 16 (Daudi-luc). The MM cell lines UM-9, generated at the University Medical Center (Utrecht, the Netherlands), 45 and L363, obtained from the ATCC and gene-marked with GFP and luciferase marker genes, 46 were transduced with human CD38 gene to obtain CD38 expression levels comparable to primary myeloma cells. For this, the amphotropic Phoenix packaging cell line (Phoenix Ampho) was transfected, using calcium phosphate precipitation, with the pQCXIN vector in which the gene encoding human CD38 was inserted.…”

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

“…When inoculating the less immunogenic MM cell line RPMI-8226/S, the GvM response was poor. Nevertheless, these mice developed GvHD, underlining that less immunogenic tumors can evade the GvM response despite the occurrence of GvHD [83]. Another xenogeneic GvM model has been described by Freeman et al After injection of GFP/luciferase-transfected human RPMI8226 human MM cells into CD122-depleted NOD-SCID mice, they obtained a MM model with bone marrow infiltration and bone lesions.…”