Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy

Area of Science:

• Immunology
• Cell Therapy
• Oncology

Background:

• Natural killer (NK) cells are a promising adoptive cell therapy for cancer due to MHC-I-independent tumor recognition and low toxicity.
• Challenges include limited in vivo persistence, tumor infiltration, and cell numbers, hindering their clinical application.

Purpose of the Study:

• To review strategies for overcoming NK cell therapy limitations.
• To highlight advancements in NK cell expansion and function enhancement for improved cancer treatment.

Main Methods:

• Optimizing NK cell expansion using feeder cells (e.g., K562) engineered with cytokines (IL-15, IL-21) and activating ligands.
• Enhancing NK cell antitumor responses through genetic modification (e.g., CAR-NK cells) and inducing memory-like NK cells.
• Investigating NK-cell-based tumor-infiltrating lymphocytes (TILs) and their association with patient survival.

Main Results:

• Engineered K562 cells facilitate massive NK cell expansion, enabling "off-the-shelf" therapy.
• Memory-like NK cells and CAR-NK cells show improved in vivo persistence, cytotoxicity, and promising clinical activity with low toxicity.
• TIL-NK cells correlate with improved survival in various solid tumors.

Conclusions:

• Diverse strategies exist for NK cell expansion and function enhancement, involving cytokines, feeder cells, and genetic modifications.
• Culturing with IL-2/IL-15 improves expansion, while IL-12/IL-21 enhances cytotoxicity.
• Advancements in NK cell expansion and clinical trials show significant potential for adoptive NK cell therapy in oncology.