Humanized Patient-Derived Xenograft (PDX) models differ from traditional PDX models because they incorporate a functional human immune system within immunocompromised mice that host the patient-derived tumors. Traditional PDX models involve implanting human tumor tissues into mice, but these models lack a human immune response, limiting their use in studying immune-based therapies. In contrast, humanized PDX models engraft human immune cells into the mice, allowing the interactions between human tumors and the immune system. This enhancement makes humanized PDX models particularly valuable for research in immuno-oncology, for the evaluation of immune-mediated side effects, and for the development of immunotherapies.

Humanized PDX model development services typically include:

• Human Immune System Reconstitution: The introduction of human immune cells, such as hematopoietic stem cells or peripheral blood mononuclear cells (PBMCs), into the mice.
• Testing different immune cell donors: Leveraging different donors allows accounting for donor variability.
• Tumor Implantation: Implanting patient-derived tumor tissues into the humanized mice.
• In Vivo Monitoring: Regular assessment of tumor growth and immune system activity within the model.
• Data Collection and Analysis: Comprehensive evaluation of tumor-immune interactions, including immune cell profiling, cytokine, Immuno-histochemistry,  body weight, and treatment response (Tumor growth Inhibition).

The development of a humanized PDX model can take several months. The process begins with humanizing the mice by engrafting them with human immune cells, which typically takes several weeks. After successful engraftment, patient-derived tumor tissues are implanted into the mice. The tumor needs additional time to grow and interact with the humanized immune system. Overall, the process from humanization to a fully developed and validated model can take between 3 to 6 months, depending on the specific requirements of the study and the tumor growth kinetics. Champions, through fully optimized workflows and continuous access to humanized mice, can offer much shorter timelines to achieve your goals faster.

Humanized PDX models are validated through several key steps:

• Immune Cell Engraftment Assessment: Confirming the presence and functionality of human immune cells within the model.
• Tumor Growth Monitoring: Observing the behavior and progression of the tumor in the presence of the human immune system to ensure it mirrors human disease.
• Treatment Response Testing: Evaluating how the model responds to therapies to ensure it accurately predicts clinical outcomes.
• Histopathological and Molecular Analysis: Conducting detailed tissue analyses to validate immune cell infiltration, tumor structure, and molecular signatures within the model.

Humanized PDX models can generate a wide array of data, including:

• Survival curves: survival experiments generating Kaplan Meyer curves comparing different treatments
• Tumor Growth Data: Metrics on tumor size and response to treatments.
• Immune Profiling Data: Detailed information on the types and activity of human immune cells within the tumor microenvironment.
• Pharmacokinetic and Pharmacodynamic Data: Insights into how drugs are metabolized and retained in the model and their effects on both the tumor and immune system.
• Histopathological Data: Microscopic analysis of tumor tissues, including immune cell infiltration and tumor architecture.
• Molecular Data: Information on gene expression, protein levels, and genetic mutations within the tumor and surrounding immune cells, aiding in the understanding of treatment mechanisms and resistance.