Table 2 Studies aimed at improving transduction efficiency in NK cells
From: Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy
Vector | Cells used for transduction | Transduction efficiency | Main findings | References |
|---|---|---|---|---|
Lentivirus | Primary NK cells | 29% (range 16–41%) with excellent viability | Multiplicity of infection (MOI) of 25 is optimal. Higher MOI results in higher transduction but lower viability. Transgene expression peaked at 5 days post-transduction and was detectable for 2 weeks | [222] |
Lentivirus | Primary NK cells and the YTS NK cell line | 98% in the YTS NK cell line, up to 80% in primary NK cells | Transduction efficiency was 20% when fresh primary NK cells were transduced without cytokines. The efficiency increased up to 20–50% when IL-2 plus IL-12 were added and 80% when PHA, a lectin, was added to the culture. The transduction efficiency remained stable in the presence of PHA for 10 days in culture | [223] |
Lentivirus | Primary NK cells | Depending on cell type, BX795 addition increased transduction efficiency up to tenfold | Inhibition of TBK1/IKKε complex by BX795 significantly improved transduction efficiency. Lentivirus RNA is probably recognized by pathways involving TBK1/IKKε complex involved in anti-viral response pathways, which may also include RIG-I, MDA-5, and TLR3 | [224] |
Lentivirus | Primary NK cells (mice) | 40% | IL-2 is not required for transduction | [225] |
mRNA transfection and lentivirus | Primary NK cells, NK-92, and NK cells from UCB | In NK-92 (56% with mRNA, 26% with lentivirus), in primary NK (approximately 10% with mRNA), and in UCB (12% to 73% with lentivirus) | mRNA delivery was more effective than lentiviral transduction in transducing the NK-92 cell line (56% vs. 26%) | [226] |
Lentivirus | NK-92, LNK, YT, and DERL7 cell lines | 15% in NK-92 and 30–40% in LNK, YT, and DERL7 cell lines | Lentiviruses are more efficient than retroviruses that require multiple rounds of transduction | [121] |
Retrovirus | Primary NK cells | 27–47% on days 5–6 of the culture and 52–75% 21 days after initial culture | MOI of 10 yields highest transfection efficiency | [227] |
Retrovirus | UCB NK cells | 49% | NK cells expressing IL-15 were detectable up to a year after infusion | [68] |
Retrovirus | UCB NK cells | 66.6% | NK cells purified from UCB and transduced with iCaspase-9, IL-15, and a CD19-specific CAR showed significant toxicity toward CD19 + tumors | [83] |