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Table 4 Comparison of virus- and non-virus mediated CAR delivery to NK cells

From: Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

Method

Advantages

Disadvantages

GMP compliance

Lentivirus

High efficiency

Potential genotoxicity owing to LTR sequences

Third generation is considered safe enough for clinical use

Favorable safety profile

Difficult to obtain high titer LV

Transduction of resting NK

Retrovirus

Long history in clinical trials

Risk of insertional oncogenesis

Compatible; successfully used to generate CAR-NK for clinical trials

Relatively easy to produce

Transgene capacity is lower than LV

Requires actively dividing cells

mRNA electroporation

Cheaper than viral production

Transient expression

Compatible

No integration risks

High transduction rates

Transposon

Transgene capacity higher than for viruses

Risk of insertion into genome

Compatible

Cheap, easy to produce

CRISPR/Cas9

Precise gene modification

Complicated to design the HDR template

Not yet applied in CAR-NK clinical trials

Ability to use endogenous promoter of choice

Efficiency is hard to control

  1. LTR: Long terminal repeat, LV: lentivirus, HDR: homology-directed repair