Ex vivo expansion of natural killer cells for hematological cancer immunotherapy: a systematic review and meta-analysis

The present systematic review aimed to investigate natural killer (NK) cell ex vivo expansion protocols within the scope of clinical trials targeting hematological cancer and to conduct a meta-analysis to assess the effect of NK cell infusion on survival. Research articles of clinical studies in which cell products produced by ex vivo expansion, consisting of a certain amount of NK cells and infused to patients with hematological cancer, were included in the systematic review. We conducted a proportion analysis with random effects for product purity and viability values. Studies having control groups were included in the survival meta-analysis. Among 11.028 identified records, 21 were included in the systematic review. We observed statistically significant heterogeneity for viability (I2 = 97.83%, p < 0.001) and purity values (I2 = 99.95%, p < 0.001), which was attributed to the diversity among isolation and expansion protocols. In addition, the survival meta-analysis findings suggested that NK cell therapy favors disease-free survival (DFS) of patients with myeloid malignancies but limited to only two clinical studies (odds ratio = 3.40 (confidence interval:1.27-9.10), p = 0.01). While included protocols yielded cell products with acceptable viability, the utility of immunomagnetic methods; feeder cells such as K562 expressing membrane-bound IL15 and 4-1BBL or expressing membrane-bound IL21 and 4-1BBL might be preferable to achieve better purity. In conclusion, NK cell therapy has a potential to improve DFS of patients with myeloid malignancies.