Hepatocellular carcinoma (HCC) has extremely poor prognosis. Immunotherapy has emerged as a new treatment for a number of cancers. Adoptive immunotherapy is one of the important cancer immunotherapy, which relies on the various lymphocytes including cytotoxic T lymphocytes, natural killer (NK) and cytokine induced killer cells. Also, there has been advance in techniques of NK cell activation to more effectively kill the cancer cells. Of note, recently the blocking antibodies targeting programmed cell death protein 1 (PD-1) have shown promising results in diverse cancers including HCC. We report our recent experience of a patient accompanying advanced HCC with extrahepatic metastases. Disease progression had occurred after sorafenib administration, while the patient showed local tumor control and tumor marker decrease by NK cell immunotherapy combined with PD-1 inhibitor therapy. Though, there was no definite survival advantage due to impaired liver function, which might be caused by treatment related toxicities as well as cancer progression.
Antibodies, Blocking ; Carcinoma, Hepatocellular ; Cell Death ; Cytokine-Induced Killer Cells ; Disease Progression ; Humans ; Immunotherapy ; Immunotherapy, Adoptive ; Killer Cells, Natural ; Liver ; Lymphocytes ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor ; T-Lymphocytes, Cytotoxic

The purpose of study was to investigate the in vitro proliferation ability of PHA-induced CIK cells and traditionally prepared CIK cells, the effector cell level and its influence on killing activity to K562 cells, and to analyze the difference between them. The peripheral blood mononuclear cells(PBMNC) of healthy persons were isolated and divided into A and B group. The CIK cells in A group were obtained by using traditional culture method, the CIK cells in B group were prepared by PHA induction. During the cultivation, the cell survival rate and cell absolute value in the cell culture system were counted every 3 days. On day 15 of culture, the cell immunophenotype of 2 groups were detected by flow cytometry, and the ratios of CD3(+)CD56(+), CD3(+)CD8(+) and CD3(+)CD4(+) cells in total cell amount of culture system were accounted. Meantime, the killing activity to K562 cells in different effector-target ratios was detected by using CCK-8 kit between the 2 groups. The results showed that the method of preparing CIK by PHA induction promoted the cell proliferation more than that of the traditional method (P < 0.05), moreover, both the survival rate of cells in 2 groups was more than 90%. The CD3(+)CD8(+), CD3(+)CD56(+) cell ratio in 2 groups obviously increased. As compared with traditional method, the CD3(+)CD8(+) cell level in B group was enhanced (P < 0.05); but there were no statistical differences in increase of CD3(+)CD56(+) cell level and decrease of CD3(+)CD4(+) cell level between 2 groups. while the effector-target ratio is 5:1, 10:1, 20:1 and 40:1, the killing activity of PHA-induced CIK cells to K562 cells was more stronger than traditionally-prepared CIK cells (P < 0.05), moreover, along with increase of effector-target ratio, the difference of killing activity to K562 cells in 2 groups significantly increased. It is concluded that compared with traditional method for preparing CIK cells, the new way by PHA induction can increase the proliferation of CIK cells obviously, enhance the ratio of CD3(+)CD8(+) cells and strengthen the killing activity to the K562 cells. This new way provides a new source of CIK cells and reliable evidence for cyto-immune therapy of leukemia and other tumors.
Cell Proliferation ; Cytokine-Induced Killer Cells ; cytology ; Humans ; K562 Cells ; Leukocytes, Mononuclear ; Phytohemagglutinins ; pharmacology

In recent years, with the incidence of malignant tumors increasing year by year, its treatment has been made great progress on the basis of traditional treatments such as surgery, radiotherapy and chemotherapy, it mainly focuses on rapid development of cellular immunotherapy. The efficacy of dendritic cells combined with cytokine induced killer cell (DC-CIK) immunotherapy for cancer patients is positive, it shows good antitumor activities and the abilities to reconstruct and enhance the immune system of tumor patients in clinical application, it has potential application value. In the treatment of hematologic malignancies which are chemotherapy-based and high-grade malignant, what is the effect of DC-CIK cells immunotherapy for them? In this review, we searched Chinese and abroad literatures from 2012 to 2018 and further focused on 18 clinical research articles about hematologic malignancies in order to analyze the characteristics of DC-CIK cells immunotherapy. It was found that DC-CIK cells can be an effective and promising treatment for patients with hematologic malignancies, and thus, if the process and unified plan are further standardized and improved, the efficacy will be more obvious. For this purpose, this paper reviews the biological characteristic of DC cells, CIK cells and the clinical research progress of DC-CIK cell immunotherapy for hematological malignancies.
Combined Modality Therapy ; Cytokine-Induced Killer Cells ; Dendritic Cells ; Hematologic Neoplasms ; Humans ; Immunotherapy ; Immunotherapy, Adoptive

Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% CD3+, 4% CD3-CD56+, 41% CD3+CD56+, 11% CD4+, and 73% CD8+. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100:1, CIK cells destroyed 51% of AsPC-1 human pancreatic cancer cells, as measured by the 51Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.
Animals ; Cytokine-Induced Killer Cells ; Humans ; Immunotherapy, Adoptive ; Mice ; Mice, Nude ; Pancreatic Neoplasms ; Transplantation, Heterologous

Hepatocellular carcinoma (HCC) has poor prognosis, even after curative resection. Early recurrence after curative treatment is a major cause of the poor prognosis. Pathologic factors such as vessel invasion, satellite nodule, size of tumor and pathologic grade are prognostic factors predicting early recurrence and poor prognosis. We share our experience of two cases which both showed early recurrence after curative hepatic resection, but eventually demonstrated different prognosis. Since the most common cause of death after potentially curative treatment is tumor recurrence, suppression of tumor recurrence might be linked to survival gain. Currently, there is no adjuvant therapy for HCC endorsed by international guidelines. However, recent studies have shown that antiviral treatment for hepatitis B virus-related HCC and immunotherapy using autologous cytokine-induced killer cell reduced HCC recurrence. Further study is needed to select patients who will benefit from adjuvant treatments.
Carcinoma, Hepatocellular* ; Cause of Death ; Cytokine-Induced Killer Cells ; Hepatectomy ; Hepatitis B ; Humans ; Immunotherapy ; Prognosis ; Recurrence

A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA). Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.
Adult ; Cytokine-Induced Killer Cells ; transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy

POEMS syndrome is a rare multiple organ involvement of the parasympathetic syndrome associated with abnormal plasma cells, mostly with high-dose chemotherapy and stem cell transplantation for the treatment. Recently, more treatment attempts to treat POEMS syndrome have been utilized so as to improve the efficacy and safety for the patients with POEMS syndrome, such as immunomodulator, alkylating agent, cytokine-induced killer cells and so on. Lenalidomide has a significant effect on relapse/refractory POEMS syndrome and patients with endocrinopathy. Cytokine-induced killer cells are also a safe and effective regimen for the treatment of POEMS syndrome. This review described the efficacy and safety of immunomodulatos, alkylators, cytokine-induced killer cells, ASCT, proteasome inhibitors and monoclonal antibodies for POEMS syndrome, and the newest clinical research and progress of POEMS syndrome ware summarized briefly.
Cytokine-Induced Killer Cells ; Humans ; Immunologic Factors ; POEMS Syndrome ; Stem Cell Transplantation ; Transplantation, Autologous

OBJECTIVETo investigate the efficiency of inducing CIK from peripheral blood mononuclear cells(PBMNC) by using immune cell serum replacement(immune cell SR), so as to provide a new strategy for the industrialized production of immune cells.

METHODSThe PBMNC of healthy volunteers were collected, and these cells were thawed after short-term cryopreservation and cultured to induce CIK cells. The cells viability was measured by trypan blue exclusion, the phenotypes were analyzed by flow cytometry, and the cytotoxicity was determined by Calcein-AM/PI double staining.

RESULTSIn cryopreserved PBMNC, the control group cells failed to normally proliferate. Cell proliferation ratio was low in 2% SR group in comparison with the fresh group, and the difference was significant (P<0.05), however, differences were not statistically significant between 5% SR and fresh group or between 10% AP and fresh group. CD3, CD3CD8 and CD3CD56 cell subsets were not significantly different before and after cryopreservation (P>0.05). After being cultured, CD3, CD3CD4, CD3CD8, CD3CD56 and CD3CD56 subsets and the cytotoxicity in vitro were not significantly different among all group(P>0.05).

CONCLUSION5% SR without the protein of animal origin can be safely used as a substitute for autologous plasma in CIK induced from cryopreserved PBMNC by culture, thus providing a basis for the application of cryopreservation technique of immune cells to cell therapy.

The treatment outcomes of relapsed or refractory neuroblastoma have been unsatisfactory till date. We reported two cases of adoptive immunotherapy using cytokine-induced killer (CIK) cells against relapsed or refractory neuroblastoma. CIK cell production was attempted in three patients, out of which two patients exhibited adequate levels of CIK cell production. Two patients completed full term of CIK cell infusions (weekly for 6 weeks and then biweekly for 8 wk) without serious adverse events. The progression-free survivals for the two patients were 1.9 and 4.1 months. Their overall survivals were 16.7 and 28.7 months. Although the efficacy was unclear, CIK cell infusion combined with other treatment strategies may have prolonged overall survival in refractory neuroblastoma patients. Further studies are needed to determine the exact role of CIK cell-based immunotherapy in relapsed or refractory neuroblastoma patients.
Cytokine-Induced Killer Cells* ; Disease-Free Survival ; Humans ; Immunotherapy* ; Immunotherapy, Adoptive ; Neuroblastoma*

Cytokine-Induced Killer Cells ; immunology ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Fetal Blood ; immunology ; HL-60 Cells ; Humans ; K562 Cells ; Killer Cells, Natural ; immunology