A single-arm phase Ib study of personalized peptide-pulsed dendritic cell-based multiple target cytotoxic T lymphocyte immunotherapy in combination with toripalimab as second-line therapy in advanced non-small-cell lung cancer.

Anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibody therapy has been approved as second-line treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, the objective response rate (ORR) is not satisfied. T lymphocytes obtained by co-culture with personalized tumor-specific antigenic peptide-pulsed dendritic cells (DC), also known as multiple target cytotoxic T lymphocytes (MCTL) can restore the antitumor immunity and potentially improve clinical outcomes. We conducted a clinical study evaluating MCTL immunotherapy combined with toripalimab in patients with advanced NSCLC. This single-center, open-label, phase Ib trial (NCT04193098) evaluated the combination of MCTL and toripalimab as second-line therapy in 21 patients with advanced NSCLC. Peripheral blood samples were collected for antigenic peptide analysis, and patient immune status was assessed. The primary and secondary endpoints were to evaluate safety and clinical outcomes, respectively. Among the 21 patients, the ORR and disease control rate (DCR) were 33.3 and 76.2%, respectively. Median overall survival (mOS) was 24.1 months, and median progression-free survival (mPFS) was 8.6 months. Most patients demonstrated improved immune status post-treatment compared to baseline. Patients exhibiting pronounced immune enhancement following MCTL/toripalimab therapy tended to have better clinical outcomes. No significant adverse events (AEs) were observed during combination therapy. In this cohort of patients with advanced NSCLC, MCTL/toripalimab therapy demonstrated manageable safety and promising antitumor efficacy as a second-line treatment. Further studies are warranted to confirm these results.