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

Abstract

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.

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

“…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.…”

Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation

“…23,24 Two phase I clinical trials (one in patients with hepatocellular carcinoma and the other in patients with Hodgkin's disease or non-Hodgkin's lymphoma) showed significant improvement in survival of patients after reinfusion of autologous CIK cells. 25,26 Another phase I clinical trial investigated repeated administration of donor-derived CIK cells in an allogeneic transplantation setting: 27 symptoms of an acute graft-versus-host disease (grade I and II) were observed in 4/11 (36%) cases and complete responses in 3/11 (27%) cases.…”

Increased survival time of a patient with metastatic malignant melanoma following immunotherapy: A case report and literature review

“…In 1991, Schmidt-Wolf et al (11) first reported that CIK cells possessed potential antitumor cell activity in the immunodeficient SCID mouse/human lymphoma model. Following this finding, additional studies indicated that CIK cells may be a better choice for patients with solid tumors and demonstrated that CIKs possess strong antitumor activity in vitro (24)(25)(26). A number of previous studies have also demonstrated that CIKs may reverse drug resistance in solid tumor cells (24)(25)(26).…”

“…Following this finding, additional studies indicated that CIK cells may be a better choice for patients with solid tumors and demonstrated that CIKs possess strong antitumor activity in vitro (24)(25)(26). A number of previous studies have also demonstrated that CIKs may reverse drug resistance in solid tumor cells (24)(25)(26). Therefore CIK cell therapy has been proposed as an alternative therapeutic strategy to adopt for patients with solid tumors.…”