Aligning preclinical AML models with immunotherapy development: principles for model selection

Area of Science:

• Hematology
• Immunology
• Cancer Research

Background:

• Immunotherapy for acute myeloid leukemia (AML) faces challenges due to the complexity of leukemic cell interactions within the bone marrow microenvironment.
• Existing preclinical models (in vitro, syngeneic, PDX, humanized) capture only partial aspects of AML biology and immune interactions.

Purpose of the Study:

• To review the evolution of preclinical models for AML immunotherapy research.
• To propose a practical, mechanism-driven framework for selecting appropriate AML models to improve clinical translatability.

Main Methods:

• Review of existing AML preclinical modeling platforms.
• Development of a framework mapping therapeutic mechanisms to model systems.
• Sequential progression from mechanistic studies to in vivo validation for model selection.

Main Results:

• Current models have limitations in replicating the dynamic interactions essential for immunotherapy efficacy.
• A proposed framework guides model selection based on specific research questions and therapeutic mechanisms.
• Emphasizes a complementary, question-driven approach leveraging diverse model strengths.

Conclusions:

• Effective preclinical modeling is essential for successful AML immunotherapy development.
• The proposed framework aids researchers in choosing models that best align with their specific therapeutic questions.
• A tailored approach to model selection enhances the translational relevance of AML immunotherapy research.