Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Natural killer (NK) cells are crucial for anti-tumor immunity.
• Enhancing NK cell efficacy against solid tumors remains a challenge.
• Chimeric antigen receptors (CARs) can redirect immune cells to target cancer.

Purpose of the Study:

• To develop and evaluate a novel CAR-NK cell therapy for metastatic colorectal cancer.
• To assess the safety and efficacy of transiently expressed NKG2D-based CAR in NK cells.

Main Methods:

• Constructed a chimeric antigen receptor (CAR) by fusing the NKG2D receptor to DAP12.
• Utilized RNA electroporation for transient CAR expression in NK cells.
• Evaluated CAR-NK cell efficacy in vitro against solid tumor cell lines and in vivo in mouse models.
• Administered CAR-NK cells locally via intraperitoneal infusion and ultrasound-guided percutaneous injection in three patients with metastatic colorectal cancer.

Main Results:

• NKG2D CAR-NK cells significantly enhanced cytolytic activity against tumor cells in vitro.
• CAR-NK cell therapy demonstrated therapeutic benefit in mice with solid tumors.
• Patients showed reduced ascites, decreased tumor cell burden, and significant tumor regression in the liver.
• Complete metabolic response was observed in treated liver lesions via PET-CT scanning.

Conclusions:

• Transiently expressed RNA CAR-NK cells are a promising strategy for enhancing anti-tumor responses.
• This approach shows significant therapeutic potential for treating metastatic colorectal cancer.
• Local infusion of CAR-NK cells can effectively target and reduce tumor burden in patients.