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Allogenic Natural Killer Cell Immunotherapy Combined with Irreversible Electroporation for Stage IV Hepatocellular Carcinoma: Survival Outcome



The study evaluates the clinical effectiveness of irreversible electroporation (IRE) in combination with immunotherapy using allogenic natural killer cells (NK) for patients with stage IV hepatocellular carcinoma (HCC). The effect of the IRE-NK enhanced immune function, decreased alpha-fetoprotein expression and showed significantly good clinical effectiveness.

Patients characteristics

40 patients with stage IV HCC age range were 31–77 years; the mean age was 55 years. Twenty-five and three patients had a history of hepatitis B and C infection, respectively. Karnofsky performance status (KPS) score ≥ 70, with no severe coronary heart disease, myelosuppression, respiratory disease, and/or acute/chronic infection, level 3 hypertension, and adequate hepatic function and renal function.


Irreversible Electroporation (IRE)
For precise monitoring of systolic blood pressure (SBP), performed invasive blood pressure measurement via the femoral artery; if the SBP was >40 mmHg during ablation or >190 mmHg at any given time, the electrical pulses were suspended for 2–3 min. If there was no obvious decrease in SBP after 2–3 min, 2–5 mg phentolamine was administered.
NK cell therapy
For NK cells culture, after isolated PBMC from whole blood, using the Human HANK Cell In vitro Preparation Kit, including the lethally radiated K562- mb15-41BBL (K562D2) stimulatory cells, plasma treatment fluid, lymphocyte culture fluid additives, serum-free medium additives and cell infusion additives. The final cell count and quality control inspection were performed at day 9 of culture.80 ml peripheral blood from allogenic donors was drawn 7 days before IRE and the immunotherapy was given 3 days after IRE.
Approximately 8-10 billion HANK cells may be harvested after culture from 80 ml of peripheral blood. After 12 days of cell culture, the NK cells were divided into three groups and intravenously infused into the patients from Day 13 to 15. Each patient must two cycles NK therapy continuously as a course.


IRE-NK therapy
All of the enrolled patients’ kinsfolk were informed, and the peripheral blood was collected for NK cell isolation 7 days before IRE. IRE was carried out on day 9, and the cultured NK cells were infused intravenously from days 13 to 15.


All hepatic lesions were treated with IRE; sessions were performed successfully. No severe complications (such as ruptured or hepatic failure, myoglobinuria, or acute renal failure) were reported post-IRE. Severalmild adverse effects occurred, but the affected patients eventually recovered with or without symptomatic management.
Clinical efficacy
We compared the lymphocyte count and function before and after treatment: The IRE-NK group had significantly higher lymphocyte subset counts after treatment, particularly NK cells; the group also had higher Th1-type cytokine levels, while that of Th2- type cytokines were largely unaffected.
Clinical outcomes
The clinical response was observed 3 months after treatment. Both groups had visibly decreased tumor volume after treatment; however, the IRE- NK group had a smaller maximum tumor diameter than the IRE group 3 months after treatment. No patient died during follow-up; six patients in the IRE group and two patients in the IRE-NK group had progressive disease (PD). The IRE-NK group had a higher disease control rate (DCR) (90%) than the IRE group (75%), but relative risk (RR) between the groups did not differ.
At the last follow-up date, the median OS in the IRE-NK and IRE group was 10.1 and 8.9 months, respectively. The IRE-NK group had significantly longer OS than the IRE group.


In summary, this single-center, retrospective study demonstrates that allogeneic NK cell therapy plus percutaneous IRE benefits outcomes and improvement for patients with hepatic cancer, which yields a substantial therapeutic pattern for stage IV HCC.

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Scientific article publishing date : 8/8/2018

Immucura identifier BSC21_191EN