IMBCR’s Core Research Services Led by James R. Berenson, M.D.

• • Biomarker & Preclinical Drug Development 
  • Our State-of-the-Art basic cancer research laboratory provides an opportunity to rapidly obtain results
  • IMBCR’s expert scientists are capable of performing a multitude of assays related to marker, biology, and drug testing of your target
  • Our specific capabilities are listed below 

  In Vitro Drug Response Analysis 🧫 Models

  • Primary cells from multiple myeloma (MM) patients
    • Bone marrow
    • Peripheral blood
  • Established multiple myeloma cell lines (e.g., MM1.S, RPMI 8226, U266)
  • Ex vivo cell culture derived from MM patients and PDX
  • 3D cell culture models(e.g., tumor spheroids) that mimic the bone marrow microenvironment more accurately than traditional 2D cultures

  💊  Drug Efficacy and Toxicity Screening

  • Assess activity of new agents
    • Alone
    • In combination with other myeloma agents
  • Anti-proliferative effects of drugs
  • Cell viability post-treatment
  • IC50 determination (median inhibitory concentration) to quantify drug potency
  • High Content Screening (HCS) to measure multiple endpoints simultaneously
  • In vitro diagnostic testing to detect measurable residual disease (MRD) in bone marrow and blood samples

  🔬 Mechanism of Action and Drug Resistance Studies

  • Investigation of drug resistance mechanisms
  • Analysis of cell cycle progression using BrdU incorporation and DAPI staining.
  • Immune cell infiltration and drug penetration studies in 3D models
  • Immunophenotyping and cytogenetic analysis
  • Integration of clinical data and genomic profiles to correlate drug response

  In Vivo Drug Response Analysis 🧬 Tumor Models

  • MM PDX (patient-derived xenograft) Models: PDX animal models uniquely derived and developed from several MM patients’ tumor samples
  • •  Complete records on patients’ background and treatment history
    • Further molecular and characterization studies of the MM PDX models
    •  Identification and recording biomarkers predicting treatment response
  • CDX (cell line-derived xenograft) Models: Established human MM cell lines (e.g., MM.1S, RPMI 8226, and U266) are used to create reproducible tumor models in mice
  • Syngeneic mouse MM models with fully functional immune systems for studying immune-tumor interactions and immunotherapies
  • Humanized mouse model with functional human immune system

  💊 Drug Efficacy and Toxicity Services

  • Single Mouse Studies for rapid screening of multiple drugs or combinations in parallel
  • Monotherapy and Combination Therapy Screening
  • • Drug Administration (IV, SC, oral, etc.)
    • Dose and Schedule Determination and Optimization
    • Tumor growth Assessment
  • Synergy/Antagonism Analysis: Using models like Bliss Independence and Chou-Talalay methods
  • Matrix Layout Testing: Systematic testing of drug combinations across dose ranges
  • Customized Protocols: Tailored to therapeutic objectives and tumor biology
  • Integration with Genomic Data: To guide rational combination strategies
  • Immune Function Analysis
  • PK/PD Analysis: Pharmacokinetics and pharmacodynamics profiling for drug metabolism and efficacy
  • Biomarker Discovery: Genomic and proteomic profiling to identify predictive biomarkers
  • Bioluminescent Imaging: For tracking tumor progression and drug response in real time

  Flow Cytometry Core Services

  🔬 1. Immunophenotyping of Plasma Cells

  • Differentiation between nonmalignant and malignant plasma cells using surface markers such as CD38, CD138, CD45, CD19, CD56, BCMA, etc.

  🧪 2. MRD Detection and Monitoring

  • Flow cytometry is used to detect MRD in bone marrow and peripheral blood, often more sensitively than conventional methods such as immunofixation
  • MRD status is a strong predictor of progression-free survival and overall survival

  🧫 3. Cell Enumeration and Subset Analysis

  • Quantification of immune cell populations including:
    • T cells, B cells, NK cells, monocytes, stromal cells, and malignant plasma cells
  • Use of fluorochrome-conjugated antibodies for multi-parametric analysis.

  🧬 4. Biomarker Profiling

  • Detection of BCMA expression and other therapeutic targets to guide treatment decisions
  • Integration with mass spectrometry for soluble BCMA (sBCMA) quantification
  • Integration of clinical data and genomic profiles to correlate drug response

  🧫 5. Sample Processing and Stability Testing

  • Standardized protocols for bone marrow aspirates (BMA) and peripheral blood (PB) using specialized tubes (e.g., Cyto-Chex®, BD TruCount™)
  • Validation of sample stability across time and temperature conditions.

  📊 6. Assay Development and Validation

  • Development of custom flow cytometry panels tailored to multiple myeloma.
  • Validation of assays for clinical trials and routine monitoring

  🧍‍♂️ 7. Gating Strategy and Data Analysis

  • Use of advanced gating hierarchies to isolate malignant plasma cells (e.g., CD45⁺CD19⁻CD56⁺BCMA⁺)
  • High intra- and inter-assay precision ensures reproducibility and reliability

  🔬 8. Histology Core Services Routine Histology Services

  • Tissue Processing & Embedding
  • Sectioning: Paraffin embedded and Frozen tissue
  • Hematoxylin & Eosin (H&E) Staining

  🧪 9. Specialized Staining Techniques

  • Special Stains: Includes Masson’s Trichrome, PAS, Oil Red O, Safranin O, Gram Stain, Picrosirius Red, and others
  • Immunohistochemistry (IHC) and Immunocytochemistry (ICC) for testing specific biomarkers
  • Immunofluorescence & Multiplex Staining

  🖥️ 10. Digital Pathology & Imaging

  • Slide Scanning: High-resolution digital imaging of stained slides.
  • Image Analysis & Quantification: Automated tools for analyzing staining patterns and tissue morphology

  🧊 11. Biorepository & Storage

  • Specimen Archiving: Long-term storage of tissue blocks and slides.
  • Temperature-Controlled Storage: Includes -80°C freezers and liquid nitrogen tanks for sample preservation

  Cell and Molecular Biology Core Services:

  🔬 12. Cell Culture & Manipulation

  • Maintenance and preparation of various cell lines
  • Cell transfection and transformation
  • Stem cell culture and differentiation
  • Viral vector production (e.g., adenovirus, AAV) for gene delivery

  13. Molecular Biology Techniques

  • DNA/RNA extraction and quantification
  • PCR, qPCR, and RT-PCR
  • Cloning and plasmid preparation
  • Gene expression analysis

  14. Proteomics & Protein Analysis

  • Western blotting
  • Protein purification and quantification
  • Enzyme assays and functional protein studies

  15. Genomics & Sequencing

  • Next-generation sequencing
  • Library preparation and bioinformatics analysis
  • Genomic data processing and interpretation

  16. Imaging & Microscopy

  • Fluorescence, confocal, and super-resolution microscopy
  • Live-cell imaging with environmental control

  17. Bioinformatics & Data Analysis

  • Custom data analysis pipelines
  • Image analysis and 3D reconstruction
  • Statistical support for experimental design

  18. Training & Consultation

  • Hands-on training on instruments and techniques
  • Experimental design consultation
  • Grant and manuscript support including proper citation of core usage

  19. Blood and Bone Marrow Samples from Patients with Plasma Cell Dyscrasias Available for Testing

  • Our biobank currently has more than 50,000 samples from more than 1,000 patients, and continues to collect specimens
  • Peripheral blood and bone marrow cells
  • Serum
  • Plasma
  • Fully characterized demographic and clinical data