UCLA researchers from the Department of Dentistry have developed an innovative method to manufacture, expand and improve the function of natural killer cells by using sonicated osteoclasts for cancer immunotherapy.
BACKGROUND: Natural killer cells (NK cells) are immune cells that recognize and combat pathogens and cancer cells. NK cell immunotherapy has emerged as a promising treatment for cancer by training NK cells to effectively eliminate tumor cells. One widely studied form of NK cell immunotherapy is adoptive cell transfer (ACT), which involves harvesting NK cells from patients, expanding them using cytokines in vitro, and then reintroducing them back into the patient to enhance cancer cell killing. However, a major limitation of this method is the difficulty in obtaining sufficient NK cell yields, especially due to contaminating T cells that outgrow NK cells in culture. This impedes therapeutic potential because effective NK cell therapies require a robust production of NK cells. One potential solution is to expand NK cells in vitro with live osteoclasts (bone-resorbing cells), but this method does not always ensure proper expansion of NK cells. In addition, co-culturing NK cells with osteoclasts requires healthy donor-derived cells, making the process costly and labor-intensive. To enhance the effectiveness of NK cell immunotherapies, it is crucial to improve methods of NK cell expansion to ensure higher yields and more efficient treatment outcomes.
INNOVATION: Researchers at UCLA led by Dr. Anahid Jewett have developed a novel in vitro method in that uses sonicated osteoclasts (sOCs) to enhance NK cell expansion and function against cancer cells. The researchers have shown that co-culturing sOCs with NK cells accelerates NK cell proliferation at a higher rate and with greater purity when compared to traditional methods using live osteoclasts. In addition, UCLA researchers have shown that this co-culturing method leads to enhanced function, as evidenced by an increase in cytokine production. With this innovation, NK cell manufacturing can be streamlined. Since sOCs can be mass-produced and stored for future use, this reduces the labor-intensive process of culturing live osteoclasts and lessens the reliance on healthy blood donations. Altogether, the use of sOCs to efficiently boost the quantity and quality of NK cells holds potential to revolutionize cancer immunotherapy, offering a scalable and effective solution to improve patient outcomes.
POTENTIAL APPLICATIONS:
- NK cell cancer immunotherapy
- Manufacturing of NK cells
- Purifying NK cells ex vivo
ADVANTAGES:
- Expanding NK cells with sOCs results in higher purity of NK cells than live osteoclasts
- sOCs can be produced in large quantities and stored, which allows for efficient manufacturing of NK cells for cancer immunotherapy
DEVELOPMENT-TO-DATE: UCLA researchers have developed a novel methodology to improve NK cell expansion and function by using sonicated osteoclasts to increase NK cell proliferation and function in vitro.
KEYWORDS: Immunotherapy, adoptive cell transfer, ACT, cytokine, natural killer cell, NK cell, sonication, osteoclast, sonicated osteoclast, sOC, cytokines, ex vivo cell expansion