CDX Models: Your Essential Guide to Smarter Cancer Drug Development

What Is a CDX Model?

In oncology research, Cell Line-Derived Xenograft (CDX) models are the go-to choice for preclinical drug evaluation. These models are created by transplanting cultured human tumor cell lines into immunodeficient mice—such as B-NDG—which lack functional T and B cells. This unique immune-compromised environment allows human tumors to grow without rejection, enabling researchers to study tumor progression in real time. By simulating human tumor growth in vivo, CDX models are invaluable for measuring anti-cancer drug efficacy, understanding tumor biology, and predicting clinical potential.

Workflow of the Cell Line-Derived Xenograft (CDX) Model (Witt and Tollefsbol 2023)

How Are CDX Models Built?

1. Animal Selection

   • Typically, 5–8-week-old immunodeficient mice are used.

   • Sex is often matched to the cancer type’s origin (e.g., female mice for breast cancer).

   • Biocytogen’s B-NDG mice are especially suited for CDX work due to their severe immunodeficiency.

2. Cell Line Selection

   • The chosen human tumor cell line must reliably form tumors in the selected mouse strain.

   • Common lines include: A549 (lung), MDA-MB-231 (triple-negative breast), HCT116 (colon), PC3 (prostate), SKOV3 (ovarian), HepG2 (liver), U87 (glioblastoma), Raji (lymphoma), and more.

3. Inoculation Methods

   • Subcutaneous (most common for easy measurement): simple, easy to monitor, uniform growth

   • Orthotopic (into the tumor’s organ of origin): models the tumor in its native microenvironment

   • Intravenous (often via tail vein or left ventricle for metastatic models): for systemic or metastatic studies

4. Tumor Growth Timeline

   • Subcutaneous tumors typically reach 50–100 mm³ in 1–2 weeks—the usual starting point for drug testing.

   • Tumor volume is tracked 2–3 times weekly.

Biocytogen’s CDX Model Library

Biocytogen offers a portfolio of over 200 fully validated CDX models spanning major cancer types—including colon, lung, breast, pancreatic, and more. Each model is supported by detailed tumor growth curves, enabling precise study planning. This comprehensive resource translates into faster study initiation, consistent model performance, and highly reproducible results.

CDX Models in Action: Case Highlights

Case #1: CAR-T Therapy Evaluation in Raji Lymphoma CDX

Four CAR-T therapies dramatically suppressed tumor growth in B-NDG mice, with excellent tolerability.

Case #2: HER2-Targeting ADC Study

Tumors with high HER2 expression responded strongly; low-HER2 tumors showed limited benefit—proving the importance of biomarker matching.

Case #3: AMG-757 Bispecific T-Cell Engager

In PBMC-reconstituted models, AMG-757 significantly reduced tumor burden in SCLC without major side effects.

AMG-757, a DLL3×CD3 bispecific T-cell engager, suppressed tumor growth in PBMC-reconstituted B-NDG MHC I/II DKO mice plus. Human PBMCs and human SCLC (SHP-77) cells were engrafted in B-NDG MHC I/II DKO mice plus. Mice received AMG-757 (1 mg/kg, i.p., QW×3) or PBS. (A) Study design; (B) Tumor volume; (C) Body weight. AMG-757 showed strong anti-tumor efficacy with good tolerability. Case #4: Lipid Nanoparticle (LNP)–mRNA Drug In this PBMC-reconstituted orthotopic liver CDX model, the positive control (LNP-mRNA drug) suppressed tumor growth with good tolerability, supporting the evaluation of novel immuno-oncology therapies. Efficacy evaluation of an orthotopic liver CDX model with immune reconstitution in B-NDG mice. Human PBMCs (5×10⁶, i.v.) were injected into B-NDG mice on Day -14, followed by orthotopic implantation of luciferase-tagged Hep 3B plus hepatocellular carcinoma cells (5×10⁵, in situ liver injection) on Day -10. Mice were randomized on Day 0 based on tumor signal and hCD45% engraftment, then treated with PBS (vehicle control) or a positive control (0.5 mg/kg, i.v., Q2D ×10). Bioluminescent imaging showed robust tumor growth in the PBS group, while the positive control significantly suppressed tumor progression. Body weight monitoring showed only minor changes over time, indicating good tolerability. Orthotopic and Metastasis Models at Biocytogen

What’s Next

With Biocytogen’s extensive CDX library, advanced mouse model platforms, and proven oncology expertise, you can accelerate your path from concept to clinic with confidence. Ready to discover how CDX models can fast-track your oncology program? Contact us for detailed growth curves, case data, and collaboration opportunities! 

FAQ:

1. Why choose a CDX model for preclinical testing?

• Rapid results: Tumors grow quickly—typically within 1–2 weeks.

• Reproducibility: Standardized cell lines lead to consistent outcomes.

• Cost-effective: Ideal for high-throughput screening and multiple treatment arms.

• Predictable scientific insight: Well-characterized lines make target validation easier. 

2. How does a CDX model differ from a PDX model?

• CDX (Cell Line–Derived Xenograft) models are created by implanting well-established human cancer cell lines into immunodeficient mice. They’re fast to establish, cost-effective, and highly reproducible—ideal for early-stage drug screening.

• PDX (Patient-Derived Xenograft) models, on the other hand, use fresh tumor tissue from patients, preserving the tumor’s genetic diversity and microenvironment. This makes them more clinically relevant for biomarker discovery and translational research, though they require more time, cost, and technical complexity.

3. Can CDX models be humanized for immuno-oncology studies?

Yes—humanized CDX models integrate human immune system reconstitution (like using PBMCs or CD34⁺ cells) into immunodeficient mice, combining tumor modeling with immune system simulation. These models are powerful for evaluating immunotherapies and studying tumor–immune interactions.

Reference:

Witt, Brittany L., and Trygve O. Tollefsbol. "Molecular, cellular, and technical aspects of breast cancer cell lines as a foundational tool in cancer research." Life 13.12 (2023): 2311.