A modifiable universal cotinine-chimeric antigen system of NK cells with multiple targets

Area of Science:

• Immunology
• Cell Therapy
• Cancer Research

Background:

• Natural killer (NK) cells are potent immune cells for adoptive immunotherapy.
• Chimeric antigen receptor (CAR) engineered cells show promise for targeted therapy.
• Limitations of current CAR therapies include heterogeneous antigen expression and tumor relapse.

Purpose of the Study:

• To develop a universal CAR-NK cell system for enhanced specificity and adaptability.
• To overcome limitations of single-antigen targeted CAR therapies.
• To create a controllable and versatile platform for cancer immunotherapy.

Main Methods:

• Designed a split and universal cotinine-CAR (Cot-CAR) system.
• Engineered NK92 cells with a CAR targeting cotinine (α-Cot-NK92 cells).
• Assessed *in vitro* cytolysis and *in vivo* lung metastasis models.

Main Results:

• The Cot-CAR system demonstrated target switching and logical response to multiple antigens.
• Engineered NK92 cells showed tunable cytolytic activity via conjugator alteration.
• The system effectively combatted tumor metastasis in a lung model.

Conclusions:

• The universal Cot-CAR system enhances antigen specificity and diversity.
• This platform combats tumor relapse and controls cytolytic activity.
• A single, integrated system provides multiple availabilities and controllability for CAR-NK therapy.