Efficacy and safety of natural killer cell therapy in patients with solid tumors: a systematic review and meta-analysis

Abstract

Introduction: In 2020, global cancer statistics reported 19.3 million new cases and 10 million deaths annually, highlighting the urgent need for effective treatments. Current therapies, such as surgery, radiation, and chemotherapy, have limitations in comprehensively addressing solid tumor. Recent advances in cancer biology and immuno-oncology, including CAR-T cell therapy, show promise but face efficacy challenges against solid tumors.

Methods: This meta-analysis systematically reviewed studies from PubMed, Embase, Cochrane, and ClinicalTrials.gov databases up to May 2024 to evaluate the clinical efficacy and safety of unmodified NK cell therapies in solid tumors. The included trials focused on reporting objective response rates (ORR).

Results: Thirty-one trials involving 600 patients across various cancers (e.g., NSCLC, HCC, breast, ovarian) were analyzed. NK cell therapies demonstrated promising ORRs, particularly 72.3% in hepatocellular carcinoma, often in combination with local therapies. Safety profiles were favorable, with fatigue being the most common adverse event.

Discussion: NK cell therapies represent a promising treatment option for solid tumors, offering a viable alternative to genetically modified cell therapies like CAR-T. Further research is needed to optimize the clinical utility of NK cell therapy and integrate it effectively into standard cancer treatment regimens.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023438410, identifier CRD42023438410.

Keywords: NK cells; killer cells; meta-analysis; natural; neoplasms; review; systematic.

Figure 1

Flow diagram representing the selection process of studies.

Figure 2

Forest plot of the overall response rate and disease control rate with 95% CI. A random effects model was applied. ORR: 0.282 (95% CI: 0.914–0.389). Heterogeneity: I2 = 77.192%; p = 0.000. DCR: 0.632 (95% CI: 0.543–0.713). Heterogeneity: I2 68.347%; p = 0.000. CRR, Complete response rate; ORR, Overall response rate.

Figure 3

Forest plot of the overall incidence AEs with 95% CI. (A). Grade 1 or 2 adverse events; (B) Grade 3 or higher adverse event.

Figure 4

Sensitivity analysis for the best overall response rate. The vertical line on the left indicated the total lower CI, the vertical line in the middle indicated the total pooled effect size and the vertical line on the right indicated the total higher CI. The circle indicated the pooled effect size after deleting the study.