Novel Mouse Model for Immune-Related Adverse Events

This invention is a non-genetic mouse model that accurately reproduces the immune-related adverse events (irAEs) seen in cancer patients undergoing immunotherapy. It is the first such model that does not require a whole gene knockout system, offering a flexible and physiologically relevant platform for studying irAEs in multiple organ systems.

Description

This mouse model faithfully recapitulates irAEs, which are common side effects in cancer patients receiving immunotherapy, by altering the diet and microbiome of the mouse. The changes in diet, specifically a Western Diet, and the microbiome lead to a baseline state of inflammation and a complex microbiota that more closely resembles a human's. This approach avoids the need for genetic modifications, meaning no genetic mutations or whole gene knockout models are required. The model is highly flexible and usable across a variety of mouse backgrounds, allowing it to be seamlessly combined with other existing genetic systems (like KO or Cre-lox systems). Furthermore, it's the first model to accurately reproduce irAEs in physiologically relevant organs, including the gut, liver, and skin.

Applications

- Immunotherapy Drug Development: Testing the safety and toxicity of new checkpoint inhibitors and other immunotherapies.
- irAE Mechanism Study: Investigating the underlying biological mechanisms and drivers of immune-related adverse events.
- Therapeutic Intervention Screening: Screening and testing novel therapeutic agents designed to mitigate or treat irAEs.
- Microbiome Research: Studying the role of the microbiome in mediating inflammatory or adverse immune responses.

Advantages

- Physiologically Relevant Adverse Events: Faithfully reproduces irAEs in physiologic organ systems, including the gut, liver, and skin, offering a more relevant preclinical model.
- Non-Genetic System: It's the first adverse event mouse model that doesn't require a whole gene knockout, simplifying model creation and reducing development time.
- Broad Compatibility: Can be used across various mouse backgrounds and seamlessly combined with other genetic systems (KO or Cre-lox) for diverse research applications.
- Human-Relevant Baseline: Achieves a more human-like baseline inflammation and complex microbiota through diet and microbiome alteration.

Invention Readiness

The development of this technology is advanced, with the concept defined, and both in vivo data and a functional prototype has been validated.

IP Status

Research Tool

Related Publication(s)

Patra D, Ye C, Rigatti L, Cillo A, Delgoffe GM, Overacre-Delgoffe AE. 1175 Deciphering immunotherapy’s challenges: a novel mouse model for immune related adverse events. Journal for ImmunoTherapy of Cancer. 2024;12:. https://doi.org/10.1136/jitc-2024-SITC2024.1175