Sensitivity of Multidrug-Resistant Tumor Cell Lines to Immunologic Effector Cells

Schmidt‐Wolf, Ingo G.H.; Lefterova, Petja; Johnston, Valerie; Scheffold, Christian; Csipai, Markus; Mehta, Bela; Tsuruo, Takashi; Huhn, D.; Negrin, Robert S.

doi:10.1006/cimm.1996.0094

Cited by 84 publications

(51 citation statements)

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“…Similar results were reported by Schmidt-Wolf et al [25] . They found that despite high cytotoxic activity of CIK against lymphoma cells, they had little toxicity against a subset of normal human hematopoietic progenitor cells.…”

Section: Discussionsupporting

confidence: 92%

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

Youshun¹

2005

WJG

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AIM:To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrugresistant (MDR) cell of HCC both in vitro and in vivo. METHODS:A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2 000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhIFN-, monoclonal anti-CD3 antibody, rhIL-1 as well as rhIL-2, which were added into the culture. To detect the cytotoxicity of the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. As to in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS:A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR; the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients receiv ed 1 -5×10 10 of CIK cell transfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION:A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.

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Section: Discussionsupporting

confidence: 92%

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

Youshun¹

2005

WJG

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“…Meanwhile, immune effector cells not only produce large amounts of inflammatory cytokines to alleviate immune damage caused by anticancer drugs and enhance the immunosurveillance capabilities of patients with cancer, 37 but additionally eliminate potential or residual tumor cells after chemotherapy, including even drug-resistant tumor cells and putative cancer stem cells. [38][39][40] Secondly, alternate application of CIK and NK cells exhibits a synergistic antitumor immunity via different mechanisms compared to the CIT with only CIK cells, which was also found by Maniar et al and Cui et al 34,35 On the other hand, it was reported that the circulating hematopoietic stem and progenitor cells from various patients with solid cancers exhibited a generalized myeloid bias with a skew toward granulocytic differentiation, 41 which increased the neutrophil-to-lymphocyte ratio (NLR), a poor prognostic indicator. 42 Adjuvant CIT could reverse the NLR, resulting in immune equilibrium to reduce tumor recurrence and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

et al. 2015

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Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients 60 y old with positive lymph nodes.

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“…Earlier work established the superiority of CIK cells over lymphokine-activated killer (LAK) cells in terms of expansion and cytotoxicity. 10,11 Potent in vitro cytotoxicity against various chemo-resistant tumour cell lines, 12 lymphoma, 10,11 and primary AML 13 and CML cells 14 had been reported. CIK cells 15,16 and other ex vivo expanded polyclonal T cells 17 have been used as an activated form of DLI in the post-allo-HSCT setting.…”

Section: Introductionmentioning

confidence: 99%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

Bone Marrow Transplant

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We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

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Sensitivity of Multidrug-Resistant Tumor Cell Lines to Immunologic Effector Cells

Cited by 84 publications

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CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

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