The global clinical trial landscape of lung cancer cellular therapy current status trends and scientific challenges

This study aims to review the development trends of clinical trials for lung cancer cellular therapy systematically, analyze the spatiotemporal distribution, research entities, cell types, target selection quantitatively, thus, trial design characteristics and reveal the evolutionary patterns, driving factors, and scientific challenges in this field. The findings are intended to provide a reference for subsequent research, policy formulation, and clinical translation.

Clinical trials of cellular therapies for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) worldwide up to July 2025 were retrieved. A cross-referencing strategy was applied to include interventional clinical studies in the process of excluding non-cellular therapies and records with missing key information. Two researchers independently screened and extracted data, 452 trials were included ultimately. Descriptive statistical methods were used to make analysis of core indicators, such as annual trends, geographical distribution, funding entities, target mechanisms, research phases, and trial status. Results Global clinical trials for lung cancer cellular therapy entered a rapid development phase, which started in 2016, peaked in 2024 (51 trials). Trials were highly concentrated on early stages, with Phase I and Phase I/II studies accounting for 79.9% (361/452). Only 7 Phase III studies were conducted, this gave a highlight of significant translational bottlenecks. Geographically, a bipolar driving pattern emerged between China and the United States. China experienced explosive growth post-2016 and leaded globally in trial numbers by 2024 (31 trials). Funding entities shifted from early public sector dominance to industry-led by small and medium-sized biotech companies. In terms of targets, PD-1 (25 trials) and IL-2Rα (22 trials) were the most popular, while emerging targets, for instance, cancer-testis antigen 1B and mesothelin gradually gained prominence. Mechanistically, immuno-oncology therapies and T-cell stimulators predominated. Among therapies such as CAR-T, NK, TCR-T, TIL, and DC vaccines, CAR-T and TIL, all showed the highest recent activity, while DC vaccines were relatively mature.

This study systematically analyzed the current status and trends of global clinical trials for lung cancer cellular therapy, which demonstrated the rapid development driven by technological breakthroughs, policy support, and capital investment. Nevertheless, lung cancer cellular therapy still faces scientific challenges, such as target selection, efficacy enhancement, and safety optimization. Future research should explore deeply to give a promotion of clinical translation and application.