A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Sponsor: Beijing YouAn Hospital

A Study of Adoptive Invariant Nature Killer T Cell Therapy for 
Relapsed/Advanced Hepatocellular Carcinoma (HCC)   
 
NCT03175679  
March 1, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Background 
Invariant Natural Killer T (iNKT) cells activated by a specific glycolipid 
antigen (a-galactosylceramide) show strong antitumor activity against 
malignant tumor through producing high levels of cytokines, such as IFN-
γ and IL-4. iNKT cells and their frequencies are abundant in the liver, but 
defect in malignant tumor development. We did a phase I dose escalation 
study with autologous in vitro expanded iNKT cells in advanced 
hepatocellular carcinoma (HCC). 
Objectives 
Inclusion criteria included diagnosed of HCC by CT or MRI, BCLC B/C 
stage, age 18 to 80 and predicted life span of 12 weeks or more to complete 
the study and follow-up. Exclusion criteria included uncontrolled systemic 
diseases, central nervous system metastases or other tumor, unstable 
immune system disease, positive HIV, syphilis or immune deficiency 
disease and known hypersensitivity immunotherapy and related drugs. All 
patient understood and voluntarily signed the informed consent. 
Method 
Patients underwent leukapheresis to collect circulating iNKT cells, which 
were isolated using a monoclonal antibody (6B11) against the invariant 
TCR-α chain expressed by iNKT cells and expanded in culture over 14 
days. The expanded cells were harvested and divided into 3 doses. The 
expansion rates of iNKT cells in enrolled patients before and after 

cultivation were analysed by flow cytometry analysis. Realtime-PCR was 
conducted to compare the mRNA level of Th1 and Th2 cytokines before 
and after iNKT cultivation. 
Stuty design 
Patients were intravenously doped with different doses of autologous iNKT 
cells, 3 infusions per course. Dosages were escalated from 3×107 cells/m2 
to at least 9×107cells/m2. Tegafur will be given twice per day for 2 weeks 
after apheresis. Human IL-2 will be given during 5-14 days after iNKT 
cells infusion. Subjects were monitored for 4 weeks post-infusion to make 
sure the safety of this therapy. The laboratory safety tests and physical 
examination were carried out at 2nd week, 4th week, 8th week and 12th 
week after iNKT infusion. All subjects were followed every 3 months until 
the disease progressed. 
 
Statistical Analysis Plan 
Means and standard deviations was used to analyze difference of expansion 
rates of iNKT cells and mRNA level of Th1 and Th2 cytokines in enrolled 
patients before and after cultivation, differences were considered 
significant for p < 0.05.