CAR T cell therapy beyond cancer: current status, challenges and future prospects

Area of Science:

• Immunology
• Cellular Therapy
• Oncology

Background:

• Chimeric antigen receptor (CAR) T-cell therapy has transformed cancer treatment.
• Its core principles are applicable to non-malignant chronic diseases driven by persistent pathological cells.

Purpose of the Study:

• To review the adaptation of CAR T-cell strategies for diverse non-malignant diseases.
• To highlight advancements in CAR T-cell engineering for enhanced efficacy and persistence.

Main Methods:

• Review of existing literature and clinical data on CAR T-cell applications in non-malignant diseases.
• Discussion of engineered CAR T-cell components like co-stimulatory domains and resistance mechanisms.
• Exploration of CAR T-cell strategies targeting specific diseases: infections, autoimmunity, fibrosis, hemophilia, transplantation, and senescence.

Main Results:

• CAR T-cell strategies show promise in treating chronic infections (HIV, EBV), autoimmune diseases, fibrosis, and senescence-associated pathologies.
• Engineered CAR T-cells with enhanced persistence and activity in suppressive microenvironments are being developed.
• Early clinical trials demonstrate feasibility and durable disease modification in conditions like lupus and multiple sclerosis.

Conclusions:

• CAR T-cell therapy offers a broadly adaptable platform for eliminating persistent pathological cells beyond oncology.
• Programmable cellular immunotherapy can remodel diseased tissue and restore immune homeostasis.
• This approach holds significant potential for treating a wide range of chronic non-malignant diseases.