A Phase IB Trial of Autologous Cytokine-Induced Killer Cells in Combination with Sintilimab, Monoclonal Antibody Against Programmed Cell Death-1, plus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.

Introduction: Can the Cytokine-induced killer (CIK) cells in combination with immune checkpoint inhibitor further improve the efficacy of chemotherapy in non-small cell lung cancer (NSCLC) patients? What are the adverse reactions of this combination therapy? But these problems are not clear. Therefore, we conducted a phase 1b trial to evaluate the safety and efficacy of autologous CIK cells therapy combined with Sintilimab, antibody against programmed cell death-1, plus chemotherapy in untreated, advanced NSCLC patients.

Patients And Methods: Patients with stage IIIB/IIIC/IV NSCLC received Sintilimab, platinum-based doublet chemotherapy, and CIK cells every 3 weeks for 4 cycles, then maintenance treatment with Sintilimab in squamous and with Sintilimab plus pemetrexed in non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.

Efficiency of Cytokine-Induced Killer Cells in Combination with Chemotherapy for Triple-Negative Breast Cancer.

Purpose: The treatment of triple-negative breast cancer (TNBC) remains challenging, due to the absence of estrogen, progesterone, and human epidermal growth factor receptors. This study was designed to evaluate the efficiency and safety of cytokine-induced killer (CIK) cell immunotherapy, following regular chemotherapy, for patients with TNBC.

Methods: A total of 340 patients with postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this retrospective study.

Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line.

Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed .

Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells.

Doxorubicin has been widely used in the treatment of cancer. However, acquired doxorubicin resistance severely hinders the application of the drug. In the present study, doxorubicin resistance was investigated in lung carcinoma.

Maintenance therapy with autologous cytokine-induced killer cells in patients with advanced epithelial ovarian cancer after first-line treatment.

Cytokine-induced killer (CIK) cells have shown cytolytic ability against ovarian cancer cells in vitro and in vivo. This study was aimed to evaluate the clinical efficacy of maintenance therapy of CIK cells in patients with advanced epithelial ovarian cancer after first-line treatment. A paired study was performed in patients with stages IIB-IV epithelial ovarian cancer after cytoreductive surgery followed by 6-8 courses of carboplatin/paclitaxel chemotherapy.

A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma.

Purpose: This prospective study aims to explore the benefit of cytokine-induced killer cell (CIK) treatment in hepatocellular carcinoma patients, which has not yet been thoroughly studied before.

Methods: From January 2004 to May 2009, 132 patients who were initially diagnosed with hepatocellular carcinoma of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, Child-Pugh scores of A or B and without prior treatment were enrolled in the study. Patients were randomly assigned to either arm 1 (n = 66) to receive CIK treatment plus standard treatment, or arm 2 (n = 66) to receive standard treatment only.

Increased prevalence of regulatory T cells in the lung cancer microenvironment: a role of thymic stromal lymphopoietin.

Expansion of CD4+CD25+ regulatory T cells (Tregs) in tumor microenvironment was one of the mechanisms by which cancer cells escaped host defense. Thymic stromal lymphopoietin (TSLP) contributes to the generation of natural Tregs in thymus. Therefore, the purpose of this report was to investigate the role of TSLP in the increasing prevalence of Tregs in lung cancer microenvironment.

Fetal-maternal microchimerism enhances the survival effect of interleukin-2-activated haploidentical peripheral blood stem cell treatment in patients with advanced solid cancer.

Killer immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction is associated with improved outcome in patients receiving hematopoietic stem cell transplants. Fetal-maternal microchimerism has been suggested to mediate acquired fetal-maternal tolerance. The goal of this study was to determine the clinical efficacy of KIR-ligand incompatibility and fetal-maternal microchimerism for interleukin-2-activated haploidentical peripheral blood stem cells (haplo-PBSCs) treatment for patients with advanced solid cancer.

Alloreactive natural killer cells promote haploidentical hematopoietic stem cell transplantation by expansion of recipient-derived CD4(+) CD25(+) regulatory T cells.

Alloreactive NK cells (Allo-NKs) have been shown to exert advantageous effects on the outcomes of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for cancer treatment. However, the mechanisms of action of Allo-NKs remain unclear. We established a novel Haplo-HSCT conditioning regimen composed of Allo-NKs and a low dose of immunosuppressive drugs (Allo-NKs + Chemo) to investigate alternative mechanisms besides direct cytotoxicity.

[A preliminary study on the effects of feto-maternal microchimerism in activated human leukocyte antigen haploidentical mobilized peripheral blood stem cells on treatment of solid tumors].

Objective: To study the effect of feto-maternal microchimerism in the treatment of activated human leukocyte antigen (HLA) haploidentical mobilized peripheral blood cells against solid tumors.

Methods: Genomic DNA samples of 25 pairs of HLA haploidentical donors and recipients were extracted. The donor-derived HLA-DRB loci were detected with nested PCR-sequence specific primer (SSP) typing.

Expression and purification of recombinant human interleukin-18 protein using a yeast expression system.

Interleukin-18 (IL-18) has been reported to exert significant immunoregulatory effects on inhibiting tumor growth through stimulating natural killer (NK) cell cytotoxicity and promoting production of several cytokines, including interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Therefore, IL-18 might serve as a potential therapeutic target for cancer treatment. However, the resource of this protein limits its availability for the clinical practice.

Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells.

Objective. To investigate the phenotype changes and proliferation activities of cytokine-induced killer cells (CIKs) and lymphokine-activated killer cells (LAKs) from healthy donor, and the cytotoxicities of CIKs and LAKs to human in vitro glioma cell lines U251 and U87. Therapy of CIK intratumoral injection was evaluated in nude mouse models.

Vaccination with allogeneic GM-CSF gene-modified lung cancer cells: antitumor activity comparing with that induced by autologous vaccine.

Objective: The aim of this study was to investigate the whole allogeneic (differing tissue-type) tumor cells as vaccine in the mouse lung cancer model. The immunogenic and antitumor activity of allogeneic vaccine was compared with that of autologous cancer cell vaccine.

Methods: C57/BL mice inoculated with Lewis lung cancer (LLC) cells were used as the animal model to test the effects of allogeneic vaccination.

[Application of low dose of fludarabine and cyclophosphamide combined with donor NK Cells as a non-myeloablative conditioning regimen for the haploidentical hematopoietic stem cell transplantation in mice].

This study was aimed to investigate the feasibility of low dose of fludarabine, cyclophosphamide combined with donor derived alloreactive NK cells as a new nonmyeloablative conditioning regimen in the haploidentical hematopoietic stem cell transplantation (haploidentical HSCT). F1 derived-NK cells were enriched with MACS magnetic separation system, in which the proportions of the Ly49C+ and Ly49A+ cells were detected by flow cytometry and the alloreactivity was measured by LDH method. The haploidentical HSCT models were constructed, and the myeloablativity in vivo, donor engraftment and the intensity of GVHD were compared between different myeloablative and nonmyeloablative conditioning regimens, including 9 Gy TBI, 6.

CD4 +CD25 + regulatory T cells decreased the antitumor activity of cytokine-induced killer (CIK) cells of lung cancer patients.

: CD(4) (+)CD(25) (+) regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro.

Th1 bias in PBMC induced by multicycles of auto-CIKs infusion in malignant solid tumor patients.

Objective: The aim of this paper was to verify the feasibility and validity of autologous cytokine-induced killer cells (Auto-CIKs) treatments in solid malignancy patients.

Methods: Amplification, phenotypic characteristics, antitumor cytotoxicity, and clinical and immunological response of Auto-CIKs derived from 66 cases of patients with solid tumor of different pathological types and at different clinical stages were examined in a large-scale clinical trail.

Results: We found that seriousness of disease and metastasis status has no influence on effective components and antitumor activity of Auto-CIKs.

[Dendritic cells reduce the number and function of CD4+CD25+ cells in cytokine-induced killer cells].

Objective: To investigate the influence of dendritic cells (DCs) on the prevalence and function of regulatory T cells (Tregs) in cytokine induced killer (CIK) cells.

Methods: The blood samples of 20 patients with solid tumors were collected. The peripheral mononuclear cells (PBMCs) were isolated.

[Study on large-scale CD34+ cell enrichment using immunomagnetic isolation apparatus].

In order to find a method suitable for purifying large amount of CD34(+) cells, from 5 cases who accepted autologous peripheral blood stem cell transplantation, CD34(+) cells were collected and enriched by using Isolex 300i (Nexell). Phenotypes were detected by flow cytometry and the biological viability were assayed by the colony-forming experiments and cell expansion experiment in vitro. The results showed that the number of mononuclear cells first collected was about (3.

Induction of specific CTL by MAGE-3/CEA peptide-pulsed dendritic cells from HLA-A2/A24(+) gastrointestinal cancer patients.

Purpose: In this study, we aimed to investigate whether MAGE3/CEA peptide-pulsed dendritic cells could induce specific cytotoxic T lymphocytes (CTL).

Methods: In this pilot study, we selected 25 patients expressing MAGE-3-HLA-A2/A24 or CEA-HLA-A24. Patients' dendritic cells (DCs) were expanded in vitro in the presence of recombined-human granular macrophage colony stimulating factor (rhGM-CSF) and recombined-human interleukin 4 (rhIL-4), pulsed with MAGE-3/CEA (HLA-A2/A24) peptide.