A phase I trial of combination CAR-NK92MI immunotherapy by dual targeting MUC-1 and PD-L1 for patients with relapsed or refractory solid tumors: focus on non-small cell lung cancer.

BACKGROUND: NK92MI cells are well-defined natural killer (NK) cell lines for tumor immunotherapy. In this study, we investigated a combination therapy of MUC-1 and PD-L1 targeted chimeric antigen receptor NK92MI (CAR-NK92MI) cells for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2016 to 2018, 7 patients with relapsed or refractory NSCLC were included in this clinical trial (ClinicalTrials.gov number, NCT02839954.Registered in 21/07/2016.). 1:1 mixed MUC-1 and PD-L1 CAR-NK92MI cells were infused, and the dosage was set at 1 × 10(8) to 2 × 10(9) CAR-NK92MI cells once. The infusion times were ranged from 3 to 37, and the median time were 22. All patients completed CAR-NK92MI cells infusion within 1 year unless intolerable toxicities appeared or disease progression (PD) occurred. RESULTS: All 7 patients were well-tolerated in the treatment. No cytokine release syndrome (CRS) and serious adverse events related to CAR-NK92MI treatment were observed. 3/7 patients achieved stable disease within more than 23 months. The median progression-free survival (PFS) was 12 months (2 to 60months) from the initial treatment, and the median overall survival (OS) was 19 months (3 to 60 months). CONCLUSION: Our results demonstrated that the combined MUC-1 and PD-L1 targeted CAR-NK92MI cell therapy is safe and efficient approach for relapsed and refractory NSCLC patients with metastasis. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov (https://classic.clinicaltrials.gov/) (NCT02839954) in 21/07/2016. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-025-03944-y.