Modeling Principle

The Mouse Raji Model is a standardized in vivo xenograft tumor model established by inoculating Epstein-Barr virus (EBV)-positive human Raji Burkitt’s lymphoma cells into severely immunodeficient mice. Derived from human Burkitt’s lymphoma, Raji cells are a classic mature suspended B-cell line with EBV genome integration and high-frequency c-Myc amplification, faithfully recapitulating the malignant biological characteristics of clinical aggressive B-cell non-Hodgkin lymphoma. This cell line presents rapid proliferation, high malignancy, stable tumorigenicity and typical drug response profiles. To avoid xenogeneic immune rejection of human lymphoma cells in immunocompetent mice, severely immunodeficient mice with combined T/B/NK cell deficiency are adopted to support stable tumor engraftment. Both subcutaneous solid lymphoma models and tail vein-disseminated systemic lymphoma models can be constructed. The subcutaneous model is suitable for high-throughput drug screening, quantitative tumor growth analysis and local pathological mechanism research; the disseminated model simulates clinical hematogenous metastasis, bone marrow infiltration, spleen involvement and systemic progression of lymphoma. This model is highly sensitive to CD20 monoclonal antibodies, BCL-2 inhibitors, BTK inhibitors, chemotherapeutic agents and novel small-molecule targeted drugs. It serves as the SCI gold-standard in vivo model for basic mechanism research, targeted efficacy verification, combination therapy optimization and preclinical translational research of Burkitt lymphoma, which can be directly applied to NSFC projects, postgraduate research proposals and standardized methodology writing of SCI manuscripts.

Model Validation

Quantitative Criteria for Tumor Formation and Growth

1. Subcutaneous model tumor formation criteria: The tumor formation rate is ≥90% within 2–3 weeks after inoculation, and local tumor volume ＞50 mm³ is defined as successful tumor formation. Tumors in the vehicle control group grow stably and continuously, with the average tumor volume reaching 600–1200 mm³ at the 3rd week after inoculation without spontaneous regression.

2. Model reproducibility criteria: The intra-group coefficient of variation (CV) of tumor volume in the vehicle control group is ＜30%, verifying standardized inoculation operation, controllable individual differences and excellent model reproducibility.

3. Disseminated model validation criteria: Human-derived CD19⁺CD45⁺ lymphoma cells can be stably detected in mouse peripheral blood, bone marrow and spleen by flow cytometry; mice present progressive weight loss and decreased activity over time with well-distinguished survival curve gradients.

4. System effectiveness criteria: The tumor growth inhibition rate (TGI) of the positive control group is ≥40% after drug intervention, or the median survival time is significantly prolonged compared with the blank model group (P＜0.05), proving that the model is sensitive to drug intervention and the pharmacodynamic evaluation system is reliable and effective.

Histopathological and Molecular Gold-Standard Indexes

1. HE staining gold standard: A large number of atypical lymphocytes with enlarged, hyperchromatic nuclei and abundant mitotic figures are observed in tumor tissues, with dense tumor cell proliferation and focal necrosis. Clear human lymphoma cell infiltration foci are detected in the spleen and bone marrow of the disseminated model, consistent with the pathological characteristics of Burkitt lymphoma.

2. Immunohistochemical phenotypic criteria: Tumor tissues present high specific expression of human CD20, positive c-Myc amplification and high Ki-67 proliferation index, perfectly recapitulating the core molecular phenotype of clinical EBV-positive Burkitt lymphoma.

3. Pharmacodynamic response criteria: Compared with the vehicle control group, the treatment group shows significantly down-regulated Ki-67 proliferation index, up-regulated Cleaved-Caspase-3 apoptotic protein and inhibited c-Myc malignant pathway expression, with restricted tumor proliferation and activated apoptosis, presenting definite in vivo pharmacodynamic phenotypes.

4. Mechanism cross-validation criteria: The molecular detection results of in vivo tissues are consistent with the pathway regulation rules of in vitro cell experiments, forming a complete evidence closed loop of "in vitro mechanism + in vivo efficacy + pathological phenotype".

Model Advantages

The Raji model is the most widely used standardized in vivo gold-standard model for global Burkitt lymphoma research with definite core advantages: clear cell line background, mature culture system, stable suspension characteristics and extremely high tumorigenicity; it naturally carries EBV integration and c-Myc amplification, fully fitting the malignant phenotype of clinical EBV-positive Burkitt lymphoma; it supports high-throughput pharmacodynamic screening of subcutaneous solid tumors and simulation of systemic disseminated diseases via tail vein injection, adapting to multi-dimensional experimental design; it presents stable and sensitive pharmacodynamic responses to CD20-targeted therapy, BCL-2 targeting, chemotherapy and combination therapy; the experimental data has high repeatability and recognition, widely accepted by mainstream SCI journals in the field of hematological oncology; the system has high standardization, fully compatible with NSFC projects, doctoral and master’s research proposals, graduation theses and SCI methodology writing, and highly compatible with the existing lymphoma/glioma model system of the research group.

Research Applications

The Mouse Raji Model is mainly used for preclinical in vivo pharmacodynamic evaluation and mechanism analysis of EBV-positive Burkitt lymphoma, widely applied to verify the in vivo anti-lymphoma activity of CD20-targeted drugs, BCL-2 inhibitors, BTK inhibitors, novel small-molecule compounds, natural anti-tumor drugs and combined chemotherapy regimens; it explores the regulatory mechanisms of lymphoma proliferation, apoptosis and malignant invasion mediated by c-Myc, NF-κB and B-cell receptor pathways. It can realize both solid tumor drug screening and systemic disseminated lymphoma disease simulation, suitable for research on lymphoma targeted drug resistance mechanism, drug synergistic mechanism and toxic safety evaluation. It fully supports basic hematological oncology research, preclinical new drug development, national and provincial project application, postgraduate proposal and dissertation writing, and SCI journal methodology construction, serving as an irreplaceable standardized gold-standard in vivo model in the field of Burkitt lymphoma research.

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