Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease

Area of Science:

• Gerontology and Neurodegenerative Diseases
• Cellular Senescence
• Immunotherapy

Background:

• Aging populations worldwide face increasing rates of neurodegenerative diseases, with Alzheimer's disease (AD) being the most common dementia.
• Senescent cells accumulate with age, promoting age-related diseases through their secretory phenotype.
• Senolytics, agents that eliminate senescent cells, are a potential anti-aging strategy.

Purpose of the Study:

• To explore the potential of cell-based therapies, inspired by chimeric antigen receptor (CAR)-T cell success, for combating aging and age-related diseases.
• To evaluate alternative CAR-based cell therapies for Alzheimer's disease, considering safety and efficacy.

Main Methods:

• Review of current research on cellular senescence and its role in aging and AD.
• Exploration of chimeric antigen receptor (CAR)-T cell therapy principles and their adaptation for aging.
• Investigation of alternative CAR-engineered cells (macrophages, regulatory T cells) and derived exosomes as potential senolytic agents.

Main Results:

• In vitro and animal models show encouraging results for cell-based approaches to target senescent cells.
• CAR-T cell therapies have demonstrated success in hematological malignancies.
• Alternative approaches like CAR macrophages, CAR regulatory T cells, and exosomes are being investigated due to CAR-T cell-related side effects and AD-specific considerations.

Conclusions:

• Cellular senescence is a key factor in aging and neurodegenerative diseases.
• While CAR-T cell therapy shows promise, its side effects and limitations in neurodegenerative conditions necessitate exploring alternatives.
• CAR macrophages, CAR regulatory T cells, and their derived exosomes represent a more promising therapeutic avenue for age-related diseases like AD.