Related Experiment Video
Updated: Jul 7, 2026
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Safety and feasibility of 5T4 antibody-coupled allogeneic NK cell therapy for solid tumors: a first-in-human phase 1
Liangjie Sun1,2, Peiwen Ma1,2, Zhenwei Miao3
1Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Patients with unresectable locally advanced or metastatic solid tumors have limited therapeutic options. Antibody-guided allogeneic natural killer (NK) cell therapy represents a novel immunotherapeutic strategy to enhance tumor targeting and cytotoxicity by coupling NK cells with tumor-specific antibodies targeting antigens such as 5T4.
Objective:
To evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of IBR854, a non-viral, non-genetically modified, 5T4 antibody-coupled allogeneic NK cell therapy, in patients with advanced solid tumors.
Patients And Methods:
This open-label, first-in-human phase 1 dose-escalation study enrolled 19 patients with unresectable locally advanced or metastatic solid tumors across five dose cohorts (3.0 × 109-12.0 × 109 cells per dose). Patients received intravenous IBR854 in a 3 + 3 escalation design. Safety, dose-limiting toxicities, adverse events, pharmacokinetics, anti-drug antibodies, and antitumor activity (RECIST v1.1) were assessed.
Results:
No dose-limiting toxicities were observed. The most common treatment-emergent adverse events were elevated interleukin levels (42.1%), infusion-related reactions (31.6%), and fever (21.1%). No anti-drug antibodies were detected. The disease control rate was 43.8%. Median progression-free survival was 43 days. Pharmacokinetic analysis based on transgene copy number showed a dose-dependent prolongation of Tmax (0.867-3.433 h), with a relatively consistent half-life (1.390-2.648 h).
Conclusions:
IBR854 demonstrated an acceptable safety and tolerability profile and achieved disease stabilization in a subset of heavily pretreated patients with advanced solid tumors. These findings support further clinical development of 5T4-targeted antibody-coupled allogeneic NK cell therapy. Trial registration This study was registered at ClinicalTrials.gov (registration number: NCT06001684).
Insights
IBR854, a novel 5T4 antibody-coupled allogeneic NK cell therapy, showed acceptable safety and disease stabilization in advanced solid tumors. Further development of this immunotherapy is supported by these promising early findings.
Area of Science:
- Immunotherapy
- Oncology
- Cell Therapy
Background:
- Limited therapeutic options exist for patients with unresectable locally advanced or metastatic solid tumors.
- Antibody-guided allogeneic natural killer (NK) cell therapy offers a novel approach to target tumors via antigens like 5T4.
Purpose of the Study:
- To assess the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of IBR854.
- IBR854 is a non-viral, non-genetically modified, 5T4 antibody-coupled allogeneic NK cell therapy.
Main Methods:
- Phase 1, open-label, dose-escalation study of IBR854 in 19 patients with advanced solid tumors.
- Intravenous administration of IBR854 across five dose cohorts using a 3+3 design.
- Evaluation of safety, dose-limiting toxicities, adverse events, pharmacokinetics, immunogenicity, and antitumor activity.
Main Results:
- No dose-limiting toxicities were observed; common adverse events included elevated interleukin levels and infusion reactions.
- No anti-drug antibodies were detected, and a disease control rate of 43.8% was achieved.
- Pharmacokinetics showed dose-dependent Tmax prolongation and a consistent half-life.
Conclusions:
- IBR854 demonstrated an acceptable safety and tolerability profile in heavily pretreated patients.
- Disease stabilization was observed in a subset of patients, supporting further clinical development.
- 5T4-targeted antibody-coupled allogeneic NK cell therapy shows potential for advanced solid tumors.
