Lymphocyte-activated killer

Ah = Antibody IL = interleukin TNF =tumornecrosis factor INF = interferon LAK =lymphocyte-activated killer CSF =colony stimulating factors and FGF = fibroblast growth factor. 

LAD Leucocyte adhesion deficiency LAK Lymphocyte-activated killer (cell) LAM, LAM-1 Leucocyte adhesion molecule, -1... 

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

Li, Q., Nagahara, N., Takahashi, H., Takeda, K., Okumura, K. (2002). Organophosphorus pesticides markedly inhihit the activities of natural killer, cytotoxic T lymphocyte and lymphocyte-activated killer a proposed inhihiting mechanism via granzyme inhibition. Toxicology 172 181-90. 

Kay, N., Allen, J., Morley, J.E., Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity, Life Sci., 35, 53, 1984. 

Merluzzi, VJ. (1985). Comparison of murine lymphokine, activated killer cells, natural killer cells, and cytotoxic T lymphocytes. Cell Immunol. 95 95-104. 

M. M. Corsi, H. H. Maes, K. Wasserman, A. Fulgenzi, G. Gaja, M. E. Ferrero, Protection by L-2-Oxothiazohdine-4-carboxyhc Acid of Hydrogen Peroxide-Induced CD3 and CD 162 Chain Down-Regulation in Human Peripheral Blood Lymphocytes and Lymphokine-Activated Killer Cells , Biochem. Pharmacol. 1998, 56, 657 - 662. 

Itoh K, Tilden AB, Kumagai K, Balch CM Leulla-F lymphocytes with natural killer activity are precursors of recombinant interleukin-2-induced activated killer cells. J Immunol 1985 134 802-807. 

Several proteins that stimulate subsets of lymphocytes involved in various aspects of the immune response are now produced by recombinant DNA techniques. The pharmacology of these lymphokines as potential anticancer agents is being investigated. Interleukin (IL) 2, originally described as a T-cell growth factor, induces the production of cytotoxic lymphocytes (lymphokine-activated killer cells, or LAK cells). IL-2 produces remissions in 10 to 20% of patients with melanoma or renal cell carcinoma when infused at high doses either alone or with lymphocytes that were previously harvested from the patient and incubated with IL-2 in vitro. 

IL-2 (Proleukin) is a cytokine that promotes the proliferation, differentiation, and recruitment of T and B lymphocytes, natural killer cells, and thymocytes. Human recombinant IL-2 is designated as rIL-2. rIL-2 binds to IL-2 receptors on responsive cells and induces proliferation and differentiation of T helper cells and T cytotoxic cells. It also can induce B-lymphocyte proliferation, activate macrophage activity, and augment the cytotoxicity of natural killer cells. 

Lipoxins have diverse effects on leukocytes, including activation of monocytes and macrophages and inhibition of neutrophil, eosinophil, and lymphocyte activation. Both lipoxin A and lipoxin inhibit natural killer cell cytotoxicity. 

In rat liver, 1,2-dimethylhydrazine had no consistent effect on the relative focal volume of y-glutamyltranspeptidase-positive preneoplastic foci (Denda et al., 1988). Locniskar et al. (1985) treated Brown-Norway and Fischer rats with 150 mg/kg bw 1,2-dimethylhydrazine by gavage five times over a three-week period. Five months after the final treatment, isolated splenic, colonic intraperithelial lymphocytes and lamina propria lymphocytes from the Brown-Norway strain exhibited low natural killer cell activity and reduced splenic T-lymphocyte proliferation in response to autologous non-T lymphocytes. Furthermore, colonic lamina propria lymphocyte proliferation was low, and Brown-Norway rats had a low incidence of 1,2-dimethylhydrazine-induced colonic neoplasms (7%) in comparison with Fischer rats, which had more effective splenic and colonic intraperithelial lymphocyte natural killer cell activity, enhanced splenic autologous mixed lymphocyte response, enhanced colonic lamina propria lymphocyte proliferation and a higher incidence of colon tumours (20%). 

Lukashev D, Ohta A, Sitkovsky M (2007) Hypoxia-dependent anti-inflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev 26(2) 273-279 MacKenzie WM, Hoskin DW, Blay J (1994) Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. Cancer Res 54(13)3521-3526... 

Cell transfer therapy is a new approach to strengthening the innate ability of the immune system to fight against cancer (Figure 51.2). In this therapy, lymphocytes are isolated and cultured with interleukin-2 for 3 d to yield lymphokine-activated killer cells, which are then administered to patients along with interleukin-2. 

IGIV Immunoglobulin intravenous LAK cell Lymphokine-activated killer cell LFA Lymphocyte functional antigen MAb Monoclonal antibody MHC Major histocompatibility complex MCP-1 Macrophage chemotactic protein-1 MIP-1 Macrophage inflammatory protein-1 NK cell Natural killer cell... 

Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon lysis of natural killer resistant fresh solid tumor cells by interleukin-2 activated autologous human peripheral blood lymphocytes. J Exp Med 1982 155 1823-41. 

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