Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma.
OBJECTIVE
To investigate the influence of autologous cytokine-induced killer (CIK) cells on the phenotypes of CIK effector cells, peripheral T lymphocyte subsets and dendritic cell subsets in patients with primary hepatocellular carcinoma (HCC).


METHODS
Peripheral blood mononuclear cells (PBMC) were collected by a blood cell separator from 13 patients with HCC, then expanded by priming them with interferon-gamma (IFN-gamma) followed by monoclonal antibody (mAb) against CD3 and interleukin-2 (IL-2) the next day. The phenotypic patterns of CIK cells were characterized by flow cytometry on d 0, 4, 7, 10, 13 and 15 of incubation, respectively. Then, 5 mL of venous blood was obtained from HCC patients before or 8-10 d after CIK cells were transfused into patients to assess the influence of CIK cells on the percentages of effector cells, and proportions of DC1 or DC2 in peripheral blood by flow cytometry.


RESULTS
After two weeks of in vitro incubation, the percentages of CD3(+)CD8(+), CD3(+)CD56(+), and CD25(+) cells increased significantly from 33.5+/-10.1%, 7.7+/-2.8%, and 12.3+/-4.5% to 36.6+/-9.0% (P<0.05), 18.9+/-6.9% (P<0.01), and 16.4+/-5.9% (P<0.05), respectively. However, the percentages of CD3(+)CD4(+) and NK cells had no significant difference. The percentages of CD3(+) and CD3(+)CD8(+) cells were kept at high levels during the whole incubation period, but those of CD25(+), and CD3(+)CD56(+) cells began to decrease on d 7 and 13, respectively. The proportions of type I dendritic cell (DC1) and type II dendritic cell (DC2) subsets increased from 0.59+/-0.23% and 0.26+/-0.12% before CIK cell therapy to 0.85+/-0.27% and 0.43+/-0.19% (all P<0.01) after CIK cell transfusion, respectively. The symptoms and characteristics of HCC patients were relieved without major side effects.


CONCLUSIONS
Our results indicated that autologous CIK cells can efficiently improve the immunological status in HCC patients, and may provide a potent approach for HCC patients as the adoptive immunotherapy.
Shi
Ming
M
Research Center of Biotherapy, Beijing Institute of Infectious Diseases, 302 Hospital of PLA, Beijing 100039, China.
Zhang
Bing
B
Tang
Zi-Rong
ZR
Lei
Zhou-Yun
ZY
Wang
Hui-Fen
HF
Feng
Yong-Yi
YY
Fan
Zhen-Ping
ZP
Xu
Dong-Ping
DP
Wang
Fu-Sheng
FS
D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000637:transplantation*; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma