Redefining cell therapy: CAR-engineered innate immune cells to conquer solid and hematologic malignancies.

Area of Science:

• Immunology
• Cellular Therapy
• Oncology

Background:

• Chimeric antigen receptor (CAR) T-cell therapy has transformed cancer treatment.
• Its application in the innate immune system remains largely unexplored.
• Innate immune cells offer unique advantages over T cells for CAR therapy.

Purpose of the Study:

• To explore the potential of CAR technology in innate immune cells for cancer therapy.
• To review recent advances in engineering innate immune cells for cancer treatment.
• To evaluate the translational progress and challenges of innate CAR-based therapies.

Main Methods:

• Review of recent scientific literature on CAR technology and innate immunity.
• Synthesis of advances in cell design, including dual/split CARs and synthetic biology circuits.
• Evaluation of translational progress, manufacturing, and regulatory aspects.

Main Results:

• Innate immune cells (NK, macrophages, γδ T, iNKT, MAIT) offer MHC-independent tumor recognition and elimination.
• These cells provide off-the-shelf manufacturing, reduced GVHD risk, and lower CRS incidence.
• CAR engineering enhances their tumor targeting, innate/adaptive crosstalk, and homing capabilities.

Conclusions:

• Integrating innate and innate-like immune cells with CAR technology creates a new generation of cellular therapeutics.
• These therapies offer broadened antigen reach, improved safety, and enhanced tumor microenvironment penetration.
• Further development is needed to overcome manufacturing and regulatory hurdles for clinical application.