Augmentative effect ofNocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s)

1989 ◽  
Vol 30 (4) ◽  
pp. 195-204
Author(s):  
Takuma Shirasaka ◽  
Ichiro Kawase ◽  
Masaji Okada ◽  
Misa Kitahara ◽  
Toshiyuki Ikeda ◽  
...  
Keyword(s):  
Cell Wall ◽  
Lak Cells ◽  
Lak Cell ◽  
Helper Factor

Lymphokine activateed killer (LAK) cell-mediated lysis of murine glioma: trypsinchymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells

1986 ◽  
Vol 372 (2) ◽  
pp. 386-389 ◽  
Author(s):  
Steven K. Jacobs ◽  
Gilbert Melin ◽  
Bud Holcomb ◽  
Catherine W. Parham ◽  
Paul L. Kornblith ◽  
...  
Keyword(s):  
Lak Cells ◽  
Selective Recognition ◽  
Lak Cell ◽  
Murine Glioma ◽  
Tumor Selective

Preclinical Evaluation of a Bone-Marrow Autograft Culture Procedure for Generating Lymphokine-Activated Killer Cells in Vitro

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 123-127 ◽  
Author(s):  
Hans-Georg Klingemann ◽  
Heather Deal ◽  
Dianne Reid ◽  
Connie J Eaves
Keyword(s):  
Bone Marrow ◽  
Calf Serum ◽  
Cell Activity ◽  
Hematopoietic Cells ◽  
Lak Cells ◽  
High Dose ◽  
Lymphokine Activated Killer Cells ◽  
Lak Cell

Despite the use of high dose chemoradiotherapy for the treatment of acute leukemia. relapse continues to be a major cause of death in patients given an autologous bone marrow transplant. Further augmentation of pretransplant chemotherapy causes life threatening toxicity to nonhematopoietic tissues and the effectiveness of currently available ex vivo purging methods in reducing the relapse rate is unclear. Recently, data from experimental models have suggested that bone marrow-derived lymphokine (IL-2)-activated killer (BM-LAK) cells might be used to eliminate residual leukemic cells both in vivo and in vitro. To evaluate this possibility clinically, a procedure was developed for culturing whole marrow harvests with IL-2 prior to use as autografts, and a number of variables examined that might affect either the generation of BM-LAK cells or the recovery of the primitive hematopoietic cells. The use of Dexter long term culture (LTC) conditions, which expose the cells to horse serum and hydrocortisone. supported LAK cell generation as effectively as fetal calf serum (FCS) -containing medium in seven-day cultures. Maintenance of BM-LAK cell activity after a further seven days of culture in the presence of IL-2 was also tested. As in the clinical setting. patients would receive IL-2 in vivo for an additional week immediately following infusion of the cultured marrow autograft. Generation ofBM-LAK activity was dependent on the presence of IL-2 and could be sustained by further incubation in medium containing IL-2. Primitive hematopoietic cells were quantitated by measuring the number of in vitro colony-forming progenitors produced after five weeks in secondary Dexter-type LTC. Maintenance of these 'LTC-initiating cells' was unaffected by lL-2 in the culture medium. These results suggest that LAK cells can be generated efficien tly in seven-day marrow autograft cultures containing IL-2 under conditions that allow the most primitive human hematopoietic cells currently detectable to be maintained.

In vitro cytolysis of primitive neuroectodermal tumors of the posterior fossa (medulloblastoma) by lymphokine-activated killer cells

1988 ◽  
Vol 69 (3) ◽  
pp. 403-409 ◽  
Author(s):  
Richard E. George ◽  
William G. Loudon ◽  
Richard P. Moser ◽  
Janet M. Bruner ◽  
Peter A. Steck ◽  
...  
Keyword(s):  
Posterior Fossa ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Mononuclear Leukocytes ◽  
Short Term ◽  
Lymphokine Activated Killer Cells ◽  
Primitive Neuroectodermal Tumors ◽  
Lak Cell ◽  
Neuroectodermal Tumors

✓ Short-term stimulation of nonantigen-primed peripheral blood mononuclear leukocytes with interleukin-2 generates a population of oncolytic effectors designated “lymphokine-activated killer” (LAK) cells. These LAK cells express potent lytic activity against a wide spectrum of fresh or cultured autochthonous (patient's own) and allogeneic (unrelated) tumors, yet specifically spare normal tissues. In this study, cells derived from primitive neuroectodermal tumors of the posterior fossa (PNET-PF) were examined for their sensitivity to LAK cytolysis utilizing an in vitro 4-hour chromium-51-release assay. Five early-passage cell lines, derived from primary PNET-PF, demonstrated significant sensitivity to LAK cell cytolysis. Lysis was equally effective in culture medium and cerebrospinal fluid. Three freshly excised PNET-PF exhibited similar susceptibility to lysis by autochthonous LAK cells. Greatly increased expansion of LAK cell cultures could be achieved by short-term stimulation with monoclonal anti-CD3 antibodies in addition to interleukin-2 activation. These findings constitute the preliminary in vitro foundations for potential intrathecal adoptive immunotherapy of PNET-PF with LAK cells.

scholarly journals Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii.

1992 ◽  
Vol 176 (6) ◽  
pp. 1511-1519 ◽  
Author(s):  
C S Subauste ◽  
L Dawson ◽  
J S Remington
Keyword(s):  
Toxoplasma Gondii ◽  
Cytotoxic Activity ◽  
Killer Cell ◽  
Lak Cells ◽  
Target Cells ◽  
Lymphokine Activated Killer Cells ◽  
Effector Cells ◽  
Lak Cell ◽  
Infected Cells ◽  
Daudi Cells

Experiments were conducted to determine whether human lymphokine-activated killer (LAK) cells are cytotoxic against cells infected with Toxoplasma gondii. Nylon wool nonadherent (NWNA) peripheral blood lymphocytes, as well as purified natural killer cell (NK) (CD3- CD16+ CD56+) and T (CD3+ CD16- CD56-) cells obtained from five healthy T. gondii seronegative volunteers exhibited minimal cytotoxic activity against T. gondii-infected cells. When standard LAK (S-LAK) cell preparations were induced by incubation of NWNA cells with recombinant interleukin 2, induction of remarkable cytotoxic activity against T. gondii-infected cells. When standard in LAK cell preparations from each of the volunteers. The phenotype of the LAK precursor and effector cells varied depending on the target cell used. Whereas the precursor and the effector cells of most of the LAK activity against K562 and Daudi cells were cells with NK phenotype, when T. gondii-infected cells were used as targets, both cells with NK and T cell phenotypes were precursors and effectors of the lysis. When cytotoxic activity of S-LAK cells was compared with the activity of adherent LAK (A-LAK) cells, A-LAK cells displayed higher cytotoxic activity against T. gondii-infected cells, as well as against K562 and Daudi cells. Cold target inhibition experiments suggested that there is a subset of LAK effector cells capable of lysing both T. gondii-infected cells and Daudi cells, whereas other subsets preferentially or exclusively lyse one of these target cells.

Augmentative effect of Nocardia rubra cell-wall skeleton (N-CWS) on lymphokine-activated killer (LAK) cell induction

1988 ◽  
Vol 26 (1) ◽  
Author(s):  
Soichiro Yokota ◽  
Takuma Shirasaka ◽  
Hideki Nishikawa ◽  
Shigeto Hosoe ◽  
Toshiyuki Ikeda ◽  
...  
Keyword(s):  
Cell Wall ◽  
Lak Cell ◽  
Cell Induction

scholarly journals Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1355-1360 ◽  
Author(s):  
F Santiago-Schwarz ◽  
C Panagiotopoulos ◽  
A Sawitsky ◽  
KR Rai
Keyword(s):  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Lymphocytic Leukemia ◽  
Lak Cell ◽  
Cell Chronic Lymphocytic Leukemia

Abstract We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B- CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B- cell growth and/or growth stimulation of the leukemic clone in B-CLL.

scholarly journals Human lymphokine activated killer (LAK) cells suppress generation of allospecific cytotoxic T cells: implications for use of LAK cells to prevent graft-versus-host disease in allogeneic bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 261-268
Author(s):  
J Uberti ◽  
F Martilotti ◽  
TH Chou ◽  
J Kaplan
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Cytotoxic T Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
Lak Cells ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Lak Cell

We have found that murine lymphokine activated killer (LAK) cells have veto and natural suppressor activities in vitro, and prevent graft- versus-host disease (GVHD) in vivo. To determine whether human LAK cells mediate veto and natural suppression we measured their ability to inhibit generation of allospecific cytotoxic T cells (CTL) in mixed lymphocyte culture (MLC). When added to MLCs at low concentrations LAK cells caused veto-type inhibition: stimulator-type LAK cells inhibited generation of CTL but responder or third-party LAK cells did not. At higher concentrations LAK cells caused nonspecific inhibition: all three LAK cell types inhibited generation of CTL. LAK cell veto and natural suppressor activities were largely eliminated by irradiation with 30 Gy and by depletion of CD56+ cells, but increased after depletion of CD3+ cells. LAK cell veto activity is not likely an artifact of cold-target inhibition by the LAK cells themselves or by proliferation of T cells contaminating LAK cell preparations: (1) veto only occurred when LAK cells were added to MLC on days 0 through 2, but not when added on day 5; (2) addition of saturating numbers of labeled targets to fixed numbers of allo-CTL effectors failed to overcome the inhibitory effects of adding stimulator-type LAK cells at the onset of MLC; and (3) CD3-depleted LAK cells showed greater veto activity than threefold greater numbers of control LAK cells. In light of our previous findings in mice, the current results imply that adoptive immunotherapy with LAK cells may be useful in preventing GVHD in human bone marrow transplant recipients.

scholarly journals Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1355-1360
Author(s):  
F Santiago-Schwarz ◽  
C Panagiotopoulos ◽  
A Sawitsky ◽  
KR Rai
Keyword(s):  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Lymphocytic Leukemia ◽  
Lak Cell ◽  
Cell Chronic Lymphocytic Leukemia

We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B- CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B- cell growth and/or growth stimulation of the leukemic clone in B-CLL.

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