Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells.
Yunmi KoYeon Ho JeongJun Ah LeePublished in: Cells (2022)
Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3 + γδTCR + Vγ9 + triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 μM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.
Keyphrases
- induced apoptosis
- single cell
- endothelial cells
- cell therapy
- recombinant human
- cell cycle arrest
- immune response
- combination therapy
- stem cells
- regulatory t cells
- oxidative stress
- cell death
- dendritic cells
- radiation therapy
- bone marrow
- photodynamic therapy
- single molecule
- endoplasmic reticulum stress
- molecularly imprinted
- inflammatory response
- cancer therapy
- high resolution
- nk cells