Effect of NK cell immunotherapy on immune function in patients with hepatic carcinoma: A preliminary clinical study

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Summary

This study investigates the effectiveness of adoptive transfer of KIR ligand-mismatched highly activated nature killer (HANK) cells in patients with hepatic carcinoma. This is the first study on the benefits of HANK cell immunotherapy for hepatic carcinoma. The observations are encouraging and imply that HANK cell immunotherapy is not only safe but can improve the immune function of patients with liver cancer and may reduce the rate of tumor metastasis and recurrence.

Patients characteristics

16 patients with clear diagnosis of primary hepatic carcinoma based on imaging and pathological findings with a median age of 53.5 years (range, 37-68 years), with tumor length of 1 to 6 cm (maximum length, <6 cm), estimated survival of > 6 months after treatment. All patients must not have serious abnormalities in liver, lung or kidney function, no ascites or brain metastasis, no high blood pressure or severe heart disease and no acute or chronic infection.
Patients were diagnosed with hepatocellular carcinoma (HCC) (n=11) or intrahepatic cholangiocellular carcinoma (ICC) (n=5). Among them, stage IV was detected in 13 patients, stage III in 2, and stage II in 1. 7 of them were Hepatitis B+.

Methodology

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 and the immunotherapy was given 3 days. 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.

Treatment

After 1 month of treatment, the WBC count and the alanine aminotransferase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine (Cr) levels were not significantly different from those before treatment. During reinfusion, the patients reported that they had no fear of cold chills, fever, or any other discomfort. Only a few patients had fever after treatment, but they underwent remission after symptomatic treatment.

Results

Changes in immune function after treatment
The absolute number of total T cells (CD3+) and NK cells (CD16+ CD56+) increased significantly after treatment. Moreover, the IL-2 and TNF-b levels increased significantly at 1 month after NK adoptive immunotherapy, but the changes in the IL-4, IL-6, IL-10 and IFN-g levels were not significant.
Clinical outcomesA total of 16 patients received different courses of immunotherapy. After follow-up for 3 months, according to the RECIST guidelines, 3 patients (18.8%) achieved partial response (PR), 8 (50%) experienced disease stabilization (SD) and 5 (31.2%) experienced disease progression (PD).
Progression-free survival
The median progression-free survival (PFS) from treatment was 7.5 months (range, 2–12 months). Despite the small number of patients enrolled, the PFS from treatment was significantly higher among patients who received more than 4 courses of NK cell transfusions (n=9) than those who received less than 4 courses.

Conclusion

This is the first study on the benefits of HANK cell immunotherapy for hepatic carcinoma These encouraging preliminary observations imply that HANK cell immunotherapy is safe, can improve the immune function of patients with liver cancer, and may even reduce the rate of tumor metastasis and recurrence.

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Scientific article publishing date 3/27/2017

Immucura identifier BSC21_263EN

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