Efficacy, Safety, and Clinical Landscape of Adoptive Cell Immunotherapy in Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Abstract

Background: Adoptive cell immunotherapy (ACI) has emerged as a promising treatment strategy for advanced (recurrent or metastatic) renal cell carcinoma (RCC), yet its clinical efficacy and safety remain unclear. This study aimed to systematically evaluate the therapeutic outcomes, safety profile, and research trends of ACI in this setting.

Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Library for relevant clinical studies. A random-effects model was used for quantitative synthesis.

Clinicaltrials: gov was also searched to assess ongoing research. Subgroup analyses were performed by geographic region and therapeutic strategy to explore heterogeneity. Publication bias was evaluated using prespecified statistical tests.

Results: A total of 1,893 studies were screened, and 30 studies involving 508 patients were included. The pooled objective response rate (ORR) for ACI monotherapy (n=12) was 12% (95% CI: 8-18%), with a progressive disease rate (PDR) of 50% (95% CI: 38-62%) and a stable disease response (SDR) of 35% (95% CI: 24-48%). Most adverse events were mild to moderate (grade 1-2), with an overall incidence of 27% (95% CI: 9-56%) for any-grade events. Subgroup analysis showed that cytokine-induced killer (CIK) cell therapy achieved the highest ORR (25%). Among 89 registered trials, a shift since 2019 was observed from non-targeted, broad-spectrum immunotherapies to targeted approaches, with CAR-T trials comprising 60% of recent studies.

Conclusions: ACI demonstrates limited efficacy and favorable safety in advanced RCC, particularly in combination strategies. Further large, well-designed trials are needed to confirm long-term benefits.