Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies

Area of Science:

• Cancer immunotherapy research
• Tumor microenvironment modeling
• Ex vivo drug testing platforms

Background:

• Adoptive cell therapies show promise for hematologic cancers but face challenges in solid tumors.
• Solid tumors impede immune cell infiltration and function due to exclusion, exhaustion, and vascular barriers.
• Current animal models have limitations for testing next-generation immune therapies in humans.

Purpose of the Study:

• To review ex vivo microphysiological systems (MPS) and microfluidic technologies for testing cell-based cancer immunotherapies.
• To explore sophisticated models that recapitulate the human tumor immune microenvironment (TIME).
• To identify strategies for predicting treatment response and overcoming resistance in solid tumors.

Main Methods:

• Examination of current strategies for testing cell-based cancer immunotherapies.
• Focus on ex vivo microphysiological systems and microfluidic technologies.
• Analysis of multicellular interactions within the tumor immune microenvironment (TIME).

Main Results:

• Microphysiological systems (MPS) can comprehensively recapitulate the human tumor immune microenvironment (TIME).
• These systems facilitate real-time prediction of treatment response and identification of prognostic assays.
• MPS enable the study of immune cell infiltration, expansion, and killing in a physiologically relevant context.

Conclusions:

• Ex vivo MPS are valuable tools for testing cell therapies against solid tumors, overcoming limitations of animal models.
• These systems can predict therapeutic vulnerabilities and biological barriers, guiding the development of novel immunotherapies.
• Insights from MPS enhance understanding of fundamental biologic mechanisms, potentially leading to treatments for incurable malignancies.