Natural Killer Cell

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Michael Boyiadzis - One of the best experts on this subject based on the ideXlab platform.

Ritsuro Suzuki - One of the best experts on this subject based on the ideXlab platform.

  • aggressive Natural Killer Cell leukemia therapeutic potential of l asparaginase and allogeneic hematopoietic stem Cell transplantation
    2012
    Co-Authors: Fumihiro Ishida, Junji Suzumiya, Won Seog Kim, Yasushi Isobe, Kazuo Oshimi, Shigeo Nakamura, Ritsuro Suzuki
    Abstract:

    We conducted a retrospective Japan-Korea multicenter study to better elucidate the clinicopathologic features and therapeutic modalities for aggressive Natural Killer Cell leukemia (ANKL). A total of 34 patients were analyzed. The median age of the patients was 40 years. Among the patients in the study, four had a history of Epstein-Barr virus-related disorders. Three types of ANKL Cells were categorized according to their morphological features. Leukemic Cells were below 20% in both peripheral blood and bone marrow of 11 patients. The clinical characteristics and prognoses of these 11 patients did not differ significantly from those of the others. As an initial therapy, l-asparaginase chemotherapy resulted in a better response. A total of six patients received allogeneic hematopoietic stem Cell transplantation (HSCT) and two received autologous HSCT, with all in non-complete remission (CR). After HSCT, four with allogeneic and one with autologous HSCT reached CR. Median survival of all patients was 51 days. Median survival for the patients with and without HSCT were 266 and 36 days, respectively. A total of two patients with allogeneic HSCT were alive and in CR. All patients without HSCT died of ANKL. The use of L-asparaginase was indicated as a factor for longer survival (HR 0.33, 95% confidence interval; 0.13-0.83, P = 0.02). Early diagnosis of ANKL, l-asparaginase-based chemotherapy and allogeneic HSCT might lead to improved patient outcomes.

  • aggressive Natural Killer Cell leukemia revisited large granular lymphocyte leukemia of cytotoxic nk Cells
    2004
    Co-Authors: Ritsuro Suzuki, Junji Suzumiya, Atsushi Notoya, Shuji Ozaki, Hisashi Gondo, H. Mori, N. Hino, Sadao Aoki, S. Nakamura, Hiroki Sugimori
    Abstract:

    Aggressive Natural Killer-Cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK Cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic Cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor Cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-Cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis.

Wing Leung - One of the best experts on this subject based on the ideXlab platform.

  • nkaml a pilot study to determine the safety and feasibility of haploidentical Natural Killer Cell transplantation in childhood acute myeloid leukemia
    2010
    Co-Authors: Jeffrey E Rubnitz, Hiroto Inaba, Raul C Ribeiro, Stanley Pounds, Barbara Rooney, Teresa Bell, Wing Leung
    Abstract:

    Purpose To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical Natural Killer (NK) Cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). Patients and Methods Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day −7) and fludarabine (25 mg/m2/d on days −6 through −2), followed by Killer immunoglobulin-like receptor–human leukocyte antigen (KIR-HLA) mismatched NK Cells (median, 29 × 106/kg NK Cells) and six doses of interleukin-2 (1 million U/m2). NK Cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mi...

  • nkaml a pilot study to determine the safety and feasibility of haploidentical Natural Killer Cell transplantation in childhood acute myeloid leukemia
    2010
    Co-Authors: Jeffrey E Rubnitz, Hiroto Inaba, Raul C Ribeiro, Stanley Pounds, Barbara Rooney, Teresa M Bell, Chinghon Pui, Wing Leung
    Abstract:

    PURPOSE To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical Natural Killer (NK) Cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). PATIENTS AND METHODS Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day -7) and fludarabine (25 mg/m(2)/d on days -6 through -2), followed by Killer immunoglobulin-like receptor-human leukocyte antigen (KIR-HLA) mismatched NK Cells (median, 29 x 10(6)/kg NK Cells) and six doses of interleukin-2 (1 million U/m(2)). NK Cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK Cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). CONCLUSION Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK Cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK Cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML.

Miroslaw J Szczepanski - One of the best experts on this subject based on the ideXlab platform.

E Nickbarg - One of the best experts on this subject based on the ideXlab platform.

  • production of Natural Killer Cell stimulatory factor interleukin 12 by peripheral blood mononuclear Cells
    1992
    Co-Authors: A Dandrea, S H Chan, D Young, M Rengaraju, Nicholas M Valiante, Jihed Chehimi, M Kubin, M Aste, M Kobayashi, E Nickbarg
    Abstract:

    Natural Killer Cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35. NKSF/IL-12 has multiple effects on T and NK Cells and was originally identified and purified from the supernatant fluid of Epstein-Barr virus (EBV)-transformed human B lymphoblastoid Cell lines. We have produced a panel of monoclonal antibodies against both chains of NKSF/IL-12. Some of these antibodies have neutralizing activity, and several combinations of them have been used to establish sensitive radioimmunoassays detecting the free p40 chain, the free p35 chain, or the p70 heterodimer. Using these reagents, we have determined that most EBV-transformed human B lymphoblastoid Cell lines constitutively produce low levels of the p70 heterodimer and an excess of the free p40 chain, whereas Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived Cell lines produce neither. Production of both p40 and p70 is increased several-fold upon stimulation of the EBV-transformed Cell lines with phorbol diesters. The ability of supernatant fluids from unstimulated and phorbol diester-stimulated Cell lines to induce interferon gamma (IFN-gamma) production from T and NK Cells, one of the effects of NKSF/IL-12, parallels the levels of production of the p70 heterodimer, known to be the biologically active form of NKSF/IL-12. Staphylococcus aureus Cowan I strain (SAC) and other stimuli induce accumulation of p40 mRNA and production of both p40 and p70 by peripheral blood mononuclear Cells (PBMC). The producer Cells appear to include both adherent Cells and nonadherent lymphocytes, possibly B Cells. The supernatant fluids from SAC-stimulated PBMC mediate the typical functions of NKSF/IL-12 (i.e., IFN-gamma induction, mitogenic effects on T/NK blasts, enhancement of NK Cell cytotoxicity) at concentrations of p70 similar to those at which recombinant NKSF/IL-12 mediates the same functions. Moreover, these activities are significantly inhibited by anti-NKSF/IL-12 antibodies. The neutralizing anti-NKSF/IL-12 antibodies also inhibit 85% of the IFN-gamma production in response to SAC, an NKSF/IL-12 inducer, and approximately 50% of the IFN-gamma production in response to non-NKSF/IL-12-inducers such as IL-2, phytohemagglutinin, and anti-CD3 antibodies. These results indicate that induced or constitutively produced NKSF/IL-12 has a major role in facilitating IFN-gamma production by peripheral blood lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

  • production of Natural Killer Cell stimulatory factor interleukin 12 by peripheral blood mononuclear Cells
    1992
    Co-Authors: A Dandrea, S H Chan, D Young, M Rengaraju, Nicholas M Valiante, Jihed Chehimi, M Kubin, M Aste, M Kobayashi, E Nickbarg
    Abstract:

    Summary Natural Killer Cell stimulatory factor (NKSF), or interleukin 12 (IL12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35 . NKSFAL12 has multiple effects on T andNK Cells and was originally identified and purified from the supernatant fluid of EpsteinBarr virus (EBV)-transformed human B lymphoblastoid Cell lines. We have produced a panel of monoclonal antibodies against both chains of NKSFAL12 . Some of these antibodies have neutralizing activity, and several combinations of them have been used to establish sensitive radioimmunoassays detecting the free p40 chain, the free p35 chain, or the p70 heterodimer. Using these reagents, we have determined that most EBVtransformed human B lymphoblastoid Cell lines constitutively produce low levels of the p70 heterodimer and an excess of the free p40 chain, whereas Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived Cell lines produce neither. Production of both p40 and p70 is increased several-fold upon stimulation of the EBVtransformed Cell lines with phorbol diesters . The ability of supernatant fluids from unstimulated and phorbol diester-stimulated Cell lines to induce interferon y (IFN-y) production from T and NK Cells, one of the effects of NKSFAL12, parallels the levels of production of the p70 heterodimer, known to be the biologically active form of NKSFAL12 . Staphylococcus aureus Cowan I strain (SAC) and other stimuli induce accumulation ofp40 mRNA and production of both p40 and p70 by peripheral blood mononuclear Cells (PBMC) . The producer Cells appear to include both adherent Cells and nonadherent lymphocytes, possibly B Cells. The supernatant fluids from SAC-stimulated PBMC mediate the typical functions of NKSFAL12 (i.e., IFN-y induction, mitogenic effects on T/NK blasts, enhancement ofNK Cell cytotoxicity) at concentrations of p70 similar to those atwhich recombinant NKSFAL12 mediates the same functions . Moreover, these activities are significantly inhibited by anti-NKSF/IL12 antibodies . The neutralizing antiNKSF/IL12 antibodies also inhibit 85% of the IFN-y production in response to SAC, an NKSF/IL 12 inducer, and approximately 50% of the IFN-y production in response to non-NKSF/IL12inducers such as IL-2, phytohemaglutinin, and anti-CD3 antibodies . These results indicate that induced or constitutively producedNKSFAL12 has a major role in facilitating IFN-y production by peripheral blood lymphocytes . Our findings that NKSFAL12 is both spontaneously produced and inducible in adherent PBMC and lymphocytes suggest that NKSFAL12 might be a major physiological regulator ofT and NK Cell function during animmune response and inflammation .

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