BACKGROUND. The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC. METHODS. In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment. RESULTS. In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months). CONCLUSION. Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1⁺ advanced NSCLC. TRIAL REGISTRATION. ClinicalTrials.gov NCT02843204. FUNDING. This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.ClinicalTrials.gov ID: NCT03180437.

Purpose This study aimed to investigate the safety and short-term efficacy of irreversible electroporation (IRE) combined with allogenic natural killer (NK) cell immunotherapy in the treatment of patients with unresectable primary liver cancer. Materials and Methods Between October 2015 and December 2016, 40 patients were enrolled and randomly allocated to either the IRE group (n = 22) or the IRE–NK group (n = 18). All adverse events experienced by the patients were recorded; the changes in tumor biomarkers [AFP, CA 19-9, circulating tumor cells (CTCs)], lymphocyte number and function, quality of life, clinical response, progression-free survival (PFS) and overall survival (OS) were assessed. Results Patients who received combination therapy exhibited significantly longer median PFS and OS than who just received IRE (PFS 15.1 vs. 10.6 months, P < 0.05, OS 17.9 vs. 23.2 months, P < 0.05). The combination therapy of IRE and NK cell immunotherapy significantly reduced CTCs and increased immune function and Karnofsky performance status. Conclusion Our data suggest a novel, promising combination therapy using IRE and allogenic NK cell immunotherapy. Larger clinical trials are required to confirm these conclusions.

Neuropathic pain (NP) is a chronic condition caused by nerve injury or disease. It remains a therapeutic challenge because conventional drugs have limited efficacy and cause adverse effects. Exosomes, with the ability to cross the blood-brain barrier, low immunogenicity, and tissue-homing capacity, have emerged as promising nanovehicles for precise microRNA (miRNA) delivery to modulate key NP pathologies such as neuroinflammation, neuronal hyperexcitability, mechanical allodynia, and thermal hyperalgesia. In this review, we highlight recent advances in exosome-mediated miRNA therapy for NP. We also elucidate the molecular mechanisms and unique advantages of exosomes as both delivery platforms and intrinsic therapeutic agents. We synthesize evidence from preclinical models and initial clinical-stage studies, addressing translational challenges in scalable production and targeted delivery. Through sustained innovation and multidisciplinary collaboration, exosome-based miRNA delivery systems demonstrate transformative potential to overcome current therapeutic limitations, enabling novel NP management strategies.