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Author Spotlight: Enhancing CAR-T Cell Function in Syngeneic Tumor Models
Published on: February 2, 2024
Humanized Mice Are Precious Tools for Preclinical Evaluation of CAR T and CAR NK Cell Therapies
Rana Mhaidly1,2,3, Els Verhoeyen1,4
1C3M, Université Côte d'Azur, INSERM, 06204 Nice, France.
Abstract:
Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for hematological malignancies. However, improvements in CAR T-cell therapies are urgently needed since CAR T cell application is associated with toxicities, exhaustion, immune suppression, lack of long-term persistence, and low CAR T-cell tumor infiltration. Major efforts to overcome these hurdles are currently on the way. Incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system and tumor tissue, represent an important fundamental and preclinical research tool. We will focus here on several CAR T and CAR NK therapies that have benefited from evaluation in humanized mice. These models are of great value for the cancer therapy field as they provide a more reliable understanding of sometimes complicated therapeutic interventions. Additionally, they are considered the gold standard with regard to assessment of new CAR technologies in vivo for safety, efficacy, immune response, design, combination therapies, exhaustion, persistence, and mechanism of action prior to starting a clinical trial. They help to expedite the critical translation from proof-of-concept to clinical CAR T-cell application. In this review, we discuss innovative developments in the CAR T-cell therapy field that benefited from evaluation in humanized mice, illustrated by multiple examples.
Insights
Humanized mice models are crucial for advancing chimeric antigen receptor (CAR) T-cell therapy by improving preclinical evaluation of safety and efficacy. These models accelerate the translation of novel CAR T-cell strategies into clinical applications for cancer treatment.
Area of Science:
- Immunology and Cancer Therapy
- Preclinical Research Models
Background:
- Chimeric antigen receptor (CAR) T-cell therapy shows promise for hematological malignancies but faces challenges like toxicity, exhaustion, and limited persistence.
- Current CAR T-cell therapies require significant improvements to overcome existing limitations and enhance patient outcomes.
Purpose of the Study:
- To review innovative developments in CAR T-cell therapy that have been significantly advanced through evaluation in humanized mouse models.
- To highlight the importance of humanized mice as a preclinical research tool for assessing novel CAR T-cell and CAR NK therapies.
Main Methods:
- Focus on CAR T-cell and CAR NK therapies evaluated in humanized mouse models.
- Discussion of how these models support the engraftment of human lymphoid systems and tumor tissues for comprehensive preclinical assessment.
Main Results:
- Humanized mice provide a more reliable platform for understanding complex therapeutic interventions.
- These models are considered the gold standard for in vivo assessment of CAR T-cell technologies, including safety, efficacy, immune response, and mechanism of action.
- Evaluation in humanized mice aids in expediting the translation of CAR T-cell therapy from proof-of-concept to clinical application.
Conclusions:
- Humanized mouse models are indispensable for the preclinical development and validation of advanced CAR T-cell therapies.
- Continued use of these models will drive innovation and improve the safety and efficacy of CAR T-cell treatments for hematological malignancies and potentially other cancers.
