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OPM-2 / OPM-2-luc Orthotopic Mouse Model Service for Multiple Myeloma (MM)

Fig 1: OPM-2 / OPM-2-luc Orthotopic Mouse Model for Multiple Myeloma (MM) preclinical research.

The OPM-2 / OPM-2-luc orthotopic mouse model for multiple myeloma engrafts a t(4;14)-positive, FGFR3-fusion human myeloma into the bone marrow of immunodeficient mice, where disseminated disease, paraprotein secretion, and osteolytic bone loss can be quantified longitudinally. Operating exclusively in preclinical oncology, Alfa Cytology delivers this xenograft platform end to end: authenticated OPM-2 / OPM-2-luc cell supply, tail-vein orthotopic inoculation into NOD/SCID or NSG hosts, scheduled imaging paired with serum human λ light chain monitoring, and terminal bone microCT and marrow flow cytometry.

Overview of OPM-2 / OPM-2-luc Orthotopic Mouse Model for Multiple Myeloma (MM)

OPM-2 is a human multiple myeloma line with a genotype that mirrors one of the disease’s most clinically important subtypes. Established in 1982 from the peripheral blood of a 56-year-old woman with myeloma in terminal leukemic phase, and distributed by DSMZ as ACC-50, the line carries the t(4;14)(p16;q32.3) translocation that fuses IGH to FGFR3 and MMSET—the cytogenetic lesion found in roughly 15–20% of myeloma patients, which confers adverse prognosis and sensitivity to proteasome inhibitor-based regimens. A deletion on chromosome 13 removes RB1, and MYC-altering aberrations contribute to an aggressive phenotype; the karyotype is hypertriploid to near-tetraploid with a modal count near 78. The cells are round to polygonal suspension cells, positive for CD38 and CD138, express cytoplasmic Igλ, and secrete a human λ light chain that serves as a serum biomarker. OPM-2 is GPRC5D-positive, making it a documented target cell for GPRC5D×CD3 bispecific antibody programs, and it is comparatively resistant to bortezomib—an asset when modeling refractory disease.

Fig 2: Reference figures for OPM-2 / OPM-2-luc cell-related literature.Fig 1. OPM2-xenograft mouse model showing MOCK-CAR, BCMA-CAR and BCMA-CST6-CAR treatment groups with bioluminescence images at days 7, 14, 21, 28 and 35, where MOCK-CAR mice developed intense whole-body signals (up to 8.0×10⁶ luminescence) while BCMA-CAR and BCMA-CST6-CAR suppressed OPM2 tumor progression, accompanied by serum CST6 elevation, reduced serum calcium and PTHrP in the BCMA-CST6-CAR group indicating osteolytic lesion protection. (Sun, Fumou, et al., 2024)

In vivo, OPM-2 supports a full menu of formats. Intravenous inoculation of 1 × 106 cells into sublethally irradiated NSG mice produces a disseminated model with tumor dissemination, paraplegia, and osteolytic bone disease at roughly eight weeks, with low inter-animal variability and robust marrow infiltration; larger 1 × 107 inocula into 200-cGy-irradiated NOD/SCID mice have powered landmark oral-dosing studies in which the BET inhibitor I-BET762 reduced serum human λ light chain, cleared bone marrow CD38+ tumor cells, and delivered a significant survival advantage. Subcutaneous formats at 106 (Matrigel-assisted) to 107 cells support rapid pharmacology screens, with validated responses to temsirolimus (ED50 near 2 mg/kg) and liposomal bortezomib; intraperitoneal injection yields a long-latency paraprotein-producing model. Luciferase-tagged derivatives (OPM-2-luc, GFP/luc formats) enable whole-animal bioluminescence tracking of skeletal burden, with ex vivo imaging and microCT confirming osteolytic lesions. Figure 1 outlines how this orthotopic system is assembled and monitored.

Cell Line Information: OPM-2 / OPM-2-luc

OPM-2’s t(4;14) genotype gives it outsized relevance in modern myeloma drug development. The defining attributes are summarized below.

Cell Line Name OPM-2; luciferase-labeled derivatives: OPM-2-luc and OPM-2-GFP/luc (commercially transduced formats, e.g., Altogen OPM2-luc)
Catalog / Accession DSMZ ACC-50
Species / Tissue / Disease Human (Homo sapiens) / peripheral blood / multiple myeloma in leukemic phase (plasma cell leukemia-like)
Origin Established in 1982 from the peripheral blood of a 56-year-old woman with IgGλ multiple myeloma in relapse, terminal leukemic phase
Defining Genetics t(4;14)(p16;q32.3) producing IGH-FGFR3 (IGH-MMSET) fusion—the lesion found in ~15–20% of MM patients with adverse prognosis; chromosome 13 deletion with RB1 loss; MYC-altering aberrations; hypertriploid/hypotetraploid karyotype with modal count 78 (range 77–82)
Immunophenotype CD38+, CD138+; cytoplasmic Igλ positive; secretes human λ light chain detectable in serum as a tumor burden biomarker; GPRC5D-positive (validated GPRC5D×CD3 bispecific target)
Morphology / Growth Single, round to polygonal suspension cells; population doubling time ~50–60 hours (slow-growing); maximal density 1.0 × 106 cells/mL
Culture Conditions RPMI-1640 + 10% heat-inactivated FBS (20% FBS for the first week after thawing, when viability may decrease); maintain 0.3–0.7 × 106 cells/mL; split 1:2 to 1:4 every 2–3 days; biosafety level 1
Authentication STR profile authenticated to the global standard ANSI/ATCC ASN-0002.1-2021; exome and RNA sequencing data available via DSMZ; mycoplasma-negative by DAPI, culture, and PCR
Drug Response Profile Comparatively bortezomib-resistant versus lines such as NCI-H929 (useful for refractory-disease modeling); validated in vivo responses to temsirolimus (s.c. format, ED50 ~2 mg/kg), liposomal bortezomib, and the oral BET inhibitor I-BET762
Model Formats (Published) NSG intravenous 1 × 106 cells (175 rads; ~8-week latency; dissemination, paraplegia, osteolytic disease); NOD/SCID intravenous 1 × 107 cells (200 cGy; treatment from day 15); subcutaneous 1 × 106 (Matrigel-assisted) to 1 × 107 cells in 50% Matrigel; intraperitoneal 1 × 107 (long-latency paraprotein model)
Imaging and Biomarker Readouts Whole-animal IVIS BLI after D-luciferin; serum human λ light chain ELISA (validated against marrow infiltration); bone marrow CD38+ human cell quantification by flow cytometry; microCT trabecular morphometry and histomorphometry (osteoclast/osteoblast counts) at endpoint
Research Applications t(4;14)/FGFR3-pathway inhibitor programs, proteasome inhibitor resistance and refractory-disease modeling, BET bromodomain and epigenetic therapy evaluation, GPRC5D and other bispecific antibody benchmarking, myeloma bone disease research, slow-release formulation and oral-dosing pharmacology

Our Services

An OPM-2 / OPM-2-luc engagement with Alfa Cytology is run as one continuous program: slow-growth-aware cell banking, route-matched orthotopic inoculation into irradiated NOD/SCID or NSG recipients, IVIS imaging paired with serum λ light chain curves, dosing per the client’s schedule, and a terminal package combining microCT bone analysis, bone marrow CD38+ flow quantification, and histomorphometry.

Workflow of OPM-2 / OPM-2-luc Orthotopic Mouse Model Construction

Building an OPM-2 or OPM-2-luc orthotopic myeloma model blends irradiation-assisted engraftment, slow-growth-aware culture, and dual imaging-plus-paraprotein readouts. The workflow below reflects the standard execution of this platform.

  1. Cell Bank Verification and Expansion: OPM-2 or OPM-2-luc stocks are authenticated by STR profiling and mycoplasma testing, then expanded slowly in RPMI-1640-based medium (20% FBS during the first week after thawing), maintained at 0.3–0.7 × 106 cells/mL to protect viability.
  2. Luciferase Calibration (OPM-2-luc Only): Signal output per cell is verified in vitro, with CD138+ identity confirmed by flow cytometry before in vivo use.
  3. Host Conditioning and Randomization: Seven- to eleven-week-old female NOD/SCID or NSG mice receive sublethal irradiation (150–240 cGy) to facilitate human cell engraftment, then are randomized by body weight under approved protocols.
  4. Orthotopic Tail-Vein Inoculation: A single-cell suspension (1 × 106 cells for the standard NSG format, up to 1 × 107 for accelerated NOD/SCID systemic models) is delivered via the tail vein so that myeloma cells home to bone marrow and skeleton.
  5. Engraftment Monitoring with Dual Readouts: Scheduled whole-animal BLI after D-luciferin tracks skeletal burden, while serial serum samples are assayed for human λ light chain; a landmark BET-inhibitor study began dosing on day 15, once disease was established.
  6. Treatment Administration: Test agents—proteasome inhibitors, FGFR3-pathway agents, BET bromodomain inhibitors, bispecific antibodies with human effector cells, or nanomedicines—are dosed orally, intraperitoneally, or intravenously per the client’s regimen.
  7. Surveillance and Survival Endpoint: Daily monitoring tracks body weight and neurological status; paraplegia, progressive weight loss, or welfare criteria define the survival endpoint for Kaplan–Meier analysis.
  8. Terminal Bone and Organ Analysis: At endpoint, vertebrae and long bones are analyzed by microCT (trabecular bone volume, osteolytic lesion counts) and histomorphometry (osteoclast/osteoblast quantification); bone marrow is profiled by flow cytometry for human CD38+ cells, and spleen and liver are imaged ex vivo.

Fig 3: Workflow for the establishment of OPM-2 / OPM-2-luc Orthotopic Mouse Models.Fig 2. OPM-2 / OPM-2-luc orthotopic mouse model construction workflow.

Case Study-OPM-2 / OPM-2-luc Orthotopic Mouse Model Development

Alfa Cytology has executed preclinical programs on the OPM-2 / OPM-2-luc orthotopic platform for clients evaluating FGFR3-pathway and BET-targeted agents, modeling bortezomib-refractory disease, benchmarking GPRC5D-directed bispecifics, and quantifying myeloma bone disease, delivering bioluminescence growth records, serum λ light chain biomarker curves, survival analyses, and microCT-supported bone assessments. As each engagement is configured around the client’s own therapeutic hypothesis, study outlines and representative datasets are available upon request.

Fig 4: Case Study-OPM-2 / OPM-2-luc Orthotopic Mouse Model Development.

Why Choose Alfa Cytology?

OPM-2 studies succeed when irradiation timing, slow culture, and dual readouts are handled as one system rather than three chores. Alfa Cytology’s integrated execution keeps the t(4;14) biology intact and the dataset complete from inoculation to bone analysis.

  • Slow-growth-aware OPM-2 / OPM-2-luc banking with thaw-viability management and density discipline.
  • Irradiation-assisted engraftment expertise across NOD/SCID and NSG formats with validated latencies.
  • Dual burden readouts: IVIS bioluminescence paired with serum human λ light chain ELISA.
  • Refractory-disease relevance: documented bortezomib-resistant phenotype for relapsed-MM modeling.
  • Terminal microCT, histomorphometry, and marrow CD38+ flow quantification in one package.
  • A dedicated team owning the study from banking through final data delivery.

Contact Us

Whether the target is FGFR3, epigenetic machinery, or refractory myeloma itself, Alfa Cytology can configure an OPM-2 / OPM-2-luc orthotopic study that answers your specific preclinical question. Contact us today to discuss study design and irradiation/engraftment parameters, or reach out to our team for a customized quotation.

Reference

  1. Sun, Fumou, et al. "BCMA-and CST6-specific CAR T cells lyse multiple myeloma cells and suppress murine osteolytic lesions." The Journal of Clinical Investigation 134.1 (2024).

For research use only. Not intended for any clinical use.

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