5 Essential Steps for a Successful Immuno-Oncology In Vivo Study

Conducting an Immuno-Oncology in vivo study is a complex process that requires meticulous planning and execution. For oncology researchers and biotech professionals, ensuring the success of these studies is crucial for advancing cancer treatments. Here are the five essential steps to guide you through a successful immuno-oncology in vivo study.

1. Select the Best Tumor Models

One of the first critical steps is choosing the appropriate tumor models. This involves:

• Molecular Data Analysis: Leverage molecular data to select tumor models that express your drug target and most closely represent the target patient population.
• Ex Vivo Screening: Utilize ex vivo screening techniques to evaluate the effectiveness of your drug in various tumor models and select models with the best response profile.

By selecting the most relevant tumor models for your immuno-oncology in vivo study, whether Patient-Derived Xenografts (PDXs) or cell lines, you can ensure that your immuno-oncology in vivo studies will provide more accurate and translatable results. Verified target expression via proteomics and genomics data, and selection of pretreated or naïve models are two extremely important elements of model selection.

2. Choose the Right Mouse Model

The choice of mouse model can significantly impact the outcomes of your immuno-oncology in vivo study. Below we provide some directions on how to navigate the different available mouse model options.

Murine immune system:

• Syngeneic Mouse Models: These are generally used when the candidate immuno-oncology drug is able to interact with the murine version of the human target. These models are generated by inoculating murine cell lines into the mice, providing a controlled environment to study immune response.

• Knock-in Humanized Mouse Models: These models are used when the candidate immuno-oncology drug only interacts with the human target molecule. These models are generated by inserting human genes into the mouse genome, allowing the candidate drug to target the murine immune response.

Humanized immune system:

• Adoptive transfer humanized models: This group of humanized mice allows for the engraftment of mature immune cells such as PBMCs and NK cells. The experimental strategy consists of engrafting human immune cells isolated from peripheral blood in immune-compromised mice to mimic some aspect of the human immune response.

• CD34 HSC humanized model: This approach provides a platform closer to the human immune system by engrafting CD34 hematopoietic stem cells (HSC) from the human cord blood. The presence of the main populations of the human immune system, including both innate and adaptive immune players, ensures an ideal platform to test a variety of immune-targeting drugs.

Selecting the right mouse model for your immuno-oncology in vivo study is crucial for understanding how your treatment will interact with the immune system. (Read our blog "Choosing the RIGHT Model - Syngeneic versus Humanized Mouse Models")

3. Evaluate Drug Toxicity

Before proceeding with efficacy studies, it's essential to evaluate the safety of your drug in the chosen mouse model system:

• Acute Toxicity Testing: Assess the immediate effects of your drug on the mouse models to identify any potential adverse reactions. Usually, a single high dose of the agent is administered to the animals, and toxicity is evaluated within 24 hours from drug administration.

• Chronic Toxicity Testing: Examine the long-term effects to ensure the drug is safe for prolonged use. In this case, animals are exposed to repeated lower doses of the candidate agent to assess toxicity over a longer period of time.

Ensuring the drug's safety through comprehensive toxicity testing is vital for the integrity of your immuno-oncology in vivo study.

4. Evaluate Tumor Killing

Next, conduct tumor-killing studies to evaluate the efficacy of your treatment:

• In Vivo Efficacy Testing: Measure the tumor size reduction and observe the mouse models' overall health.
• Comparison Studies: Compare your drug’s performance with existing treatments to establish its effectiveness and advantage over standard of care therapies.

These studies will provide concrete evidence of your immuno-oncology drug's potential to kill cancer cells, a fundamental step before moving to the clinical research stage.

5. Analyze the Mechanism of Drug Action

Understanding how your drug works at a molecular level is the final step to creating a successful immuno-oncology in vivo study.

• Flow Cytometry: Use flow cytometry to analyze the types and states of cells affected by your treatment. This analysis will reveal the effects of your candidate drug on the number, proliferation, and activation of the different immune cells. (Read our blog "Using Flow Cytometry as an In Vivo Study Endpoint")
• RNA Sequencing (RNA-seq): Perform RNA-seq to examine gene expression changes induced by your drug. Complementary to flow cytometry, RNA-seq, and DRUG-seq can expose the on-target and off-target effects of your candidate drug, possibly revealing new therapeutic and synergistic opportunities. (Read our blog "Exploring DRUG-seq: Revolutionizing RNA-seq in Oncology Research")

These analyses will give you insights into the precise mechanisms through which your immuno-oncology drug operates, paving the way for further development and optimization.

By following these five essential steps, you can enhance the accuracy, efficacy, and safety of your immuno-oncology in vivo study. At Champions Oncology, we are committed to supporting researchers with cutting-edge tools and expertise.

Ready to take your research to the next level? Reach out to our team of experts and see how we can help you achieve groundbreaking results.