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

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). 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 × 108 to 2 × 109 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. 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). 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. Our study was registered in ClinicalTrials.gov ( https://classic.clinicaltrials.gov/ ) (NCT02839954) in 21/07/2016.