Expansion of cytotoxic CD3+ CD56+ cells from peripheral blood progenitor cells of patients undergoing autologous hematopoietic cell transplantation

Alvarnas, Joseph; Linn, Yeh-Ching; Hope, Ernest G; Negrin, Robert S.

doi:10.1053/bbmt.2001.v7.pm11349808

Cited by 75 publications

(59 citation statements)

References 22 publications

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“…Compared to NK cells taken from healthy donors and expanded, killer cells derived from CLL patients appeared to be equally cytotoxic after expansion ex vivo. 33 In conclusion, our results clearly demonstrate that several potentially cytolytic subtypes of lymphocytes from B-CLL patients can be expanded in vitro. These cells express CD16 and Granzyme B and have cytolytic capacity, indicating that their use alone or in combination with Mab may be a feasible clinical strategy for controlling B-CLL.…”

Section: Expansion Of Killer Cells From Patients With B-cllsupporting

confidence: 61%

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Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy

et al. 2003

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B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world. It is currently an incurable disease, making new treatment options such as immunotherapy desirable. Monoclonal antibodies (Mabs) to surface antigens of the tumor cell is one option. Administration of cytotoxic cells such as natural killer (NK) and natural killerlike T (NKT) cells expanded in vitro might be a useful treatment modality alone or in combination with MAbs. A limiting step in the development of successful cellular immunotherapy has been the availability of appropriate cytotoxic cells. Here, we report the feasibility of expanding populations of the human killer cells, CD3ÀCD56 þ NK and CD3 þ CD56 þ NKT cells, from peripheral blood mononuclear cells (PBMCs) of B-CLL patients. The influence of tumor B cells on the in vitro expansion of killer cells was assessed by depleting B cells from PBMCs by microbead separation before culture. The 21-day cultures from both B-cell-and non-B-cell-depleted PBMC showed a marked expansion of NK cells, and also of T cells, among which almost half had the NKT phenotype. Depletion of B cells before culture did not change the expansion rates of NK and NKT cells significantly. In patients with progressive B-CLL, NK cell expansion capacity was improved after fludarabine treatment when compared to samples obtained before treatment. Repeated samples of PBMCs from individual untreated patients with both indolent and progressive disease cultured under identical conditions gave similar NK cell expansion rates. Expanded killer cell populations had cytotoxic function against the NK-sensitive target K562 cell line and expressed high levels of Granzyme B. From our studies, we conclude that NK cells as well as NKT cells from the peripheral blood of B-CLL patients can be expanded, and that these cells have cytotoxic capacity.

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Section: Expansion Of Killer Cells From Patients With B-cllsupporting

confidence: 61%

“…30 In that report, the T cells that expanded in vitro partly coexpressed the NK marker CD56. Moreover, the expansion of CD3 þ CD56 þ T cells from normal donors, 31 patients with CML, 32 and patients undergoing autologous hematopoietic cell transplantation 33 has also been reported.…”

Section: Discussionmentioning

confidence: 96%

Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy

et al. 2003

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“…A number of studies [20,21] have illuminated that CIK possessed much stronger cytotoxicity than LAK to several kinds of cancer such as leukemia, renal cell carcinoma, melanoma [22] , and proved that dendritic cells increased in serum of host after transfusion of CIK to HCC patients. Here we demonstrated CIK cells from HCC patients could equally kill drug-resistant HCC cell line as those from normal.…”

Section: Discussionmentioning

confidence: 99%

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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“…Cell cultures were prepared for flow cytometric phenotypic analysis and four-color fluorescence was performed according to standard procedures (16). Briefly, 10 5 CIK cells derived from PBMCs of donors suspended in 50 µl PBS were stained with 10 µl fluorochrome-conjugated monoclonal antibodies (1:50; BD Biosciences, Franklin Lakes, NJ, USA) against CD3 (cat.…”

Section: Cellmentioning

confidence: 99%

“…A protocol has been established previously to rapidly and reproducibly expand CIK cells in vitro from human peripheral blood (13)(14)(15)(16). In the present study, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine (termed Gao Dong, GD) (17), a novel TLR7 agonist, was combined with the traditional protocol of culturing CIK cells to determine the role of GD in the activation of CIK/NK cells.…”

Section: Introductionmentioning

confidence: 99%

Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

Gao

Cai²,

Chen

et al. 2018

Oncol Lett

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Abstract. Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio-or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-me thoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells. The proportion of GD-induced CD3 + CD56 + CIK and CD3 -CD56 + NK cells was ~4% higher respectively compared with the control. Notably, combination therapy with CIK/NK cells stimulated by GD, markedly suppressed the proliferation of the chronic myelogenous leukemia K562 cell line. Following GD treatment, the cytotoxicity improved by ~25 and 21% when the effector/target ratio was 20:1 and 10:1, respectively. The results of the present study suggested a novel protocol for CIK/NK cell proliferation and revealed that GD may serve as a potent innate and adaptive immunomodulator in immunocyte culture.

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Expansion of cytotoxic CD3+ CD56+ cells from peripheral blood progenitor cells of patients undergoing autologous hematopoietic cell transplantation

Cited by 75 publications

References 22 publications

Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy

Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy

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

Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

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