Abstract A044: Meta-analysis of adoptive natural killer cell transfer immunotherapy against solid cancers in human patients

Abstract Purpose: Recent studies revealed innate lymphoid cells (ILCs) to play critical roles in tumor pathogenesis across multiple preclinical cancer models, however their potential therapeutic efficacy in human cancer patients remain largely unclear. Natural killer (NK) cells, the founding members of group 1 ILCs, exhibit potent anti-tumor cytotoxic activities and NK cell adoptive transfer may serve as a promising immunotherapeutic strategy against solid cancers in patients, however to date this has not been conclusively demonstrated. Methods: A prospectively registered systematic review and meta-analysis (registration ID: CRD42024523774) was conducted assessing the safety and efficacy of NK cell-based adoptive transfer immunotherapies in patients with solid cancers. Major databases including Medline, Embase and Scopus were searched, and all controlled clinical trials utilising NK cell adoptive transfer in patients with solid cancers were included. Results: Of the 4597 articles screened, 44 clinical trials that utilise NK cell-based adoptive transfer therapies in patients with solid cancers were identified, of which 15 were controlled clinical trials and were included in the study. Combined meta-analysis of patients with advanced neuroblastoma, pancreatic, renal, liver, brain, colorectal and lung cancers treated with adoptive NK cell transfer together with standard treatment revealed a 44% and 67% increase in overall clinical response rate (RR=1.44; 95% CI 1.18-1.75, I2=0%, P<0.0001) and complete response rate (RR=1.67, 95% CI 1.02-2.74, I2=0%, P=0.04) respectively, compared to standard treatment alone. Strikingly, the addition of adoptive NK cell transfer immunotherapy reduced the disease progression rate by 53% (RR=0.47, 95% CI 0.34-0.66, I2=0%, P<0.0001), improved progression-free survival by an average of 2.87 months (95% CI=0.58-5.15, I2=0%, P=0.01), and was not associated with increased haematological or systemic adverse effects such as anaemia (P=0.30) and fever (P=0.13). Conclusions: The present study is the first meta-analysis to demonstrate that the addition of adoptive NK cell transfer immunotherapy to existing standard treatment is safe and efficacious in improving clinical response rate and prolonging survival in patients with solid cancers. Citation Format: Eric Jou, Jamie SY Ho. Meta-analysis of adoptive natural killer cell transfer immunotherapy against solid cancers in human patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A044.