CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Natural killer (NK) cells possess potent antitumor capabilities.
• Adoptive NK cell therapy for solid tumors is limited by poor tumor infiltration.
• Chemokines and their receptors are crucial for immune cell distribution and therapeutic targeting.

Purpose of the Study:

• To investigate the role of the CCR5-CCL5 axis in NK cell homing to tumor sites.
• To enhance NK cell infiltration and antitumor activity through genetic modification and oncolytic virus therapy.
• To evaluate the synergistic efficacy of combining CCR5-engineered NK cells with CCL5-expressing oncolytic vaccinia virus.

Main Methods:

• Analyzed CCR5 expression on NK cells from cancer patients and healthy donors.
• Upregulated CCR5 on NK cells and CCL5 in tumor cells using lentiviral and oncolytic viral vectors.
• Conducted in vitro and in vivo experiments using engineered NK cells and CCL5-expressing oncolytic vaccinia virus.

Main Results:

• Low CCR5 expression was observed on NK cells from patients with solid tumors and healthy subjects.
• CCR5-engineered NK cells demonstrated improved tumor infiltration and antitumor effects in vivo, but not complete regression.
• CCL5-expressing oncolytic vaccinia virus enhanced NK cell accumulation within tumor lesions and improved therapeutic efficacy without compromising NK cell function.

Conclusions:

• Enhancing chemokine receptor expression on NK cells and utilizing oncolytic viruses to deliver chemokines can significantly improve NK cell homing to tumors.
• This combined strategy offers a promising approach to augment NK cell-based cancer therapy for solid tumors.
• Oncolytic vaccinia viruses expressing chemokines synergize with NK cells to enhance antitumor immune responses.