OBJECTIVE@#To evaluate the
safety and
efficacy of allogeneic natural killer (NK)
cells in the
treatment of primary
hepatocellular carcinoma (HCC), and to elucidate the mechanism of
NK cells therapy.@*
METHODS@#Twenty-one
patients with primary HCC treated with allogeneic
NK cells at the Fifth Medical Center of the PLA
General Hospital were followed up for 1 year.
Peripheral blood mononuclear cells (PBMCs) were isolated from
patient-related
donors and cultured
in vitro for 15 days and infused to the
patients in two consecutive days. Clinical data and
laboratory data were collected and analyzed, including
survival, clinical features, imaging changes,
hematology,
immunology, and biochemical
indicators to evaluate the
safety and
efficacy of allogeneic
NK cell therapy. The changes of peripheral
blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-
tumor mechanisms.@*RESULTS@#(1) Of the 21
patients with primary HCC, 11
patients were treated once, 5
patients were treated twice, and 5
patients were treated 3 times. After allogeneic
NK cells infusion, 10
patients had
fever, 1
patient had slight hepatalgia and 1
patient had slight
headache, no other adverse events occurred including acute and
chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other
treatment. (2) The total
disease control rate was 76.2% during one-year follow-up. Among them, the
patients with Barcelona clinic
liver cancer (BCLC) stage A had a
disease control rate of 100%, stable
disease (SD) in 10 cases; BCLC stage B
patients had a
disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C
patients had a
disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of
NK cells and CD8+
T cells in peripheral
blood were significantly lower than that before at 24 hours
after treatment, and the frequencies of CD4+
T cells and CD4/CD8 were significantly higher than the baseline.@*CONCLUSION@#Allogeneic
NK cells have good
safety and
efficacy in the
treatment of primary HCC. The anti-
tumor effect of the allogeneic
NK cells may
play an important
role in the activation of the
patient's natural
immune system and delay
disease progression, suggesting that allogeneic
NK cells combined with
sorafenib may be a very effective
treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.