Disease relevance of Killer Cells, Lymphokine-Activated

• None of 11 patients treated with interleukin-2 but not LAK cells had hypothyroidism [1].
• Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2 [2].
• A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells, compared with those who received IL-2 alone (24-month survival: 32% versus 15%; 48-month survival: 18% versus 4%; P2 = .064 [corrected]) [3].
• STUDY OBJECTIVE: To determine the incidence, clinical magnitude, and risk factors for nosocomial bacteremia in patients given interleukin-2 with or without (+/-) lymphokine activated killer (LAK) cells for cancer immunotherapy [4].
• The treatment of cancer with lymphokine-activated killer (LAK) cells in conjunction with high-dose interleukin-2 (IL-2) has been limited by the toxicity of IL-2 and the narrow range of tumors that respond to therapy [5].

High impact information on Killer Cells, Lymphokine-Activated

• Gzm B is a neutral serine protease with Aspase activity that is found only in the granules of activated cytolytic T cells, natural killer cells, and lymphokine-activated killer cells [6].
• These findings may not only explain previous reports of transformation of CTL into NK-like "lymphokine-activated killers" (LAK cells) under high doses of IL2 (a substitute for IL15) but may also have significant implications for understanding and treating immunopathological diseases [7].
• The murine nonclassical class I major histocompatibility complex-like CD1.1 molecule protects target cells from lymphokine-activated killer cell cytolysis [8].
• Furthermore, anti-beta treatment of the K562 and A549 tumor cell lines inhibited NK (by > 95%) and interleukin 2-activated killer (LAK) cell (by 75%) cytotoxicity, respectively [9].
• No significant changes in the susceptibility of cell lines overexpressing hsp70 or hsp27 to cytotoxicity mediated by LAK cells were observed [10].

Chemical compound and disease context of Killer Cells, Lymphokine-Activated

• All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity [11].
• Generation and partial characterization of melanoma sublines resistant to lymphokine activated killer (LAK) cells. Relevance to doxorubicin resistance [12].
• Tamoxifen (TX) and toremifene (TO) enhanced the lysis of P815 mastocytoma cells in vitro by syngeneic DBA2 spleen cells that have been activated by human recombinant interleukin-2 (IL-2) for 6 days (lymphokine-activated killer [LAK] cells) [13].
• This study analyses the ability of all-trans retinoic acid (RA) to alter both sICAM and mICAM-1 expression in C8161 and Hs294T human melanoma cell lines and investigates the involvement of ICAM-1 in the interaction between tumour and lymphokine-activated killer (LAK) cells using the Cr-51 release assay [14].
• Paradoxical effects of 5-FU/folinic acid on lymphokine-activated killer (LAK) cell induction in patients with colorectal cancer [15].

Biological context of Killer Cells, Lymphokine-Activated

• RESULTS: Butyrate increased lymphokine-activated killer cell sensitivity and expression of major histocompatibility complex class I and intercellular adhesion molecule 1 in vitro [16].
• Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells [17].
• Inhibition of the growth of normal granulocyte-macrophage colonies by CD2+ LAK cells is blocked by antibodies to the CD2-lymphocyte function-associated antigen 3 (LFA-3) (CD58) cell adhesion system [18].
• 2. Although the murine orthologue of human granzyme H has not yet been identified, murine granzymes C, D, E, F, and G also lie between the murine granzyme B and cathepsin G genes on murine chromosome 14; murine granzymes C, D, and F are also highly expressed in LAK cells, but minimally in cytotoxic T lymphocytes (CTL) [19].
• Activation of ADCC was detected earlier than lymphokine activated killer cell (LAK) activity, required less IL-2 for optimum induction (50 versus 1000 units/ml), and was of equal or greater absolute magnitude (+10 to +200%) against the cell lines tested [20].

Anatomical context of Killer Cells, Lymphokine-Activated

• Several granule mediators of cytotoxicity, including a pore-forming protein (perforin), and a family of serine esterases, have been isolated from cytotoxic T lymphocytes (CTL), lymphokine-activated killer (LAK) cells, and natural killer (NK) cells [21].
• Lymphocytes, which appeared morphologically to be activated, were present at the site of regressing tumor, and it appears that the mechanism of the antitumor effect of recombinant IL-2 administered systemically is via the generation of LAK cells in vivo, although this hypothesis remains to be proven [22].
• Administration of increasing doses of recombinant IL-2 intraperitoneally resulted in the generation of LAK cells in the spleens of recipient mice [22].
• We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells [23].
• 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 [24].

Associations of Killer Cells, Lymphokine-Activated with chemical compounds

• LAK cells generated from tumor-bearer splenocytes had effects equivalent to those from normal animals, and this antimetastatic effect of the LAK cells did not require the prior administration of cyclophosphamide or other immunosuppressants [25].
• Pretreatment of human peripheral blood lymphocytes (PBL) with cisplatin (CDDP) before in vitro culture with interleukin-2 (IL-2) inhibited the generation of lymphokine-activated killer (LAK) cells and strongly inhibited proliferation [26].
• Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions [27].
• Moreover, the combination of IL-2 excipient and LAK cells or IL-2 and irradiated LAK cells did not produce a fluid leak [28].
• In vitro L-arginine enhanced natural-killer (NK) and lymphokine-activated-killer (LAK) cell activity; this cytotoxicity was mediated by CD56+ cells [29].

Gene context of Killer Cells, Lymphokine-Activated

• In contrast to IL-2, BSF-1 failed to induce an LAK cell population, as detected with Daudi tumor targets, in cultures that had not been allosensitized [30].
• IL-7 was found to induce the generation of both CTL and LAK cells in bulk cultures [31].
• Both nonadherent and adherent populations of LAK cells express IL-1 beta mRNA; however, the adherent population produced more IL-1 beta mRNA and maintained its expression for a prolonged period of time [32].
• The purpose of the studies reported here is to determine whether interleukin 1 (IL-1) plays an important role in the regulation of lymphokine-activated killer (LAK) cell induction [33].
• These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells [34].

Analytical, diagnostic and therapeutic context of Killer Cells, Lymphokine-Activated

• We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available [35].
• These findings provide a rationale for clinical trials of the infusion of human LAK cells generated with recombinant IL-2 as well as Phase I trials of the infusion of recombinant IL-2 systemically into humans [2].
• Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal [36].
• Twenty-eight cancer patients were treated for 5 consecutive days with low-dose rIL-2, followed by leukapheresis, infusion of LAK cells, and prolonged IL-2 administration [37].
• Implementation of this procedure could eliminate the high cost of cell culture which normally accompanies IL-2/LAK cell therapy [38].

References