Lymphocyte-activated killer cells

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). 

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. 

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%). 

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. 

IL-2 is a lymphokine produced by activated helper T-lympho-cytes. It induces the proliferation of T cells and promotes the differentiation of lymphocytes into cytotoxic cells. IL-2 also induces interferon gamma production (Lewko and Oldham, 2003). Activation of peripheral leukocytes with the drug produces lymphokine-activated killer cells (LAK) that lyse a variety of tumor cells in vitro. IL-2 has been cloned in bacteria through recombinant DNA technology, thus allowing the production of large amounts. IL-2 alone or with LAK cells can cause regression of several established metastatic tumors in animals (Lewko and Oldham, 2003 Dorr, 1993). 

Kawakami Y, Klein TW, Newton C, Djeu JY, Specter S, Friedman H (1988b) Suppression by delta-9-tetrahydrocannabinol of interleukin 2-induced lymphocyte proliferation and lymphokine-activated killer cell activity. Int J Immunopharmacol 10 485-488... 

Incubation of human lymphocytes with 0.1-01.0 pg/mL benzo[a]pyrene resulted in a suppression of lymphokine-activated killer cell (LAK) activity against tumor targets after 3 and 7 days (Lindemann... 

Exercise poses a stress on the immune system however, moderate chronic exercise may enhance positive immune functions. Severe or intense long-term exercise may compromise the immune system by suppressing concentrations of lymphocytes, natural-killer cell activity, lymphocyte proliferation, and secretory IgA. During the period of immune impairment ( open window"), microbial agents may invade the host and cause infections. The changes in immune functions, lower exercise capacity, and nutritional factors in the elderly may lead to a greater and longer open window period, increased risk of infections which may contribute to morbidity and mortality. 

Abbreviations Con A, concanavalin A CTL, cytotoxic T lymphocytes IL, interleukin iNOS, inducible nitric oxide synthase KLH, keyhole-limpet hemocyanin LAK, lymphokine-activated killer cell NHEK, normal human epidermal keratinocyte NK, natural killer cell PFC, plaque-forming cell SRBC, sheep red blood cell TNF, tumor necrosis factor. 

Aldesleukin (IL-2) and several other interleukins activate natural killer cells (NK cells) and lymphokine-activated killer cells (LAK cells promiscuous killers ). The investigational use of aldesleukin in AIDS patients is partly based on the fact that lymphocytes from such individuals produce significantly less IL-2 than lymphocytes from healthy controls. The answer is (A). RhJD) immune globulin contains antibodies against Rh (D) antigens. Administration to an Rh-negative mother within 72 hours after the birth of an Rh-positive baby prevents Rh hemolytic disease of the newborn (erythroblastosis fetalis) in subsequent pregnancies. The answer is (D). 

Adoptive therapy attempts to overcome blocks to the efferent arm of the immune system by harvesting immune cells from the patient, manipulating them to activate them or otherwise increase their effectiveness and then re-infusing them to target the tumor. Classically, the cell types used have included peripheral blood mononuclear cells (PBMC), lymphokine-activated killer cells (LAK), tumor infiltrating lymphocytes (TIL), and cytotoxic lymphocytes (CTL). 

In mice with immune suppression induced by cyclophosphamide, intraperitoneal administration of 2.5, 25, or 250 mg/kg of reishi polysaccharides daily for 7 days enhanced the function of immunological effector cells. The 2.5 mg/kg dose accelerated recovery of bone marrow cells, red blood cells, white blood cells, splenic natural killer cells, and natural killer T cells, and enhanced T and B cell proliferation responses, cytotoxic T lymphocyte activity, and NK cell and lymphokine activated killer cell activity (Zhu etal. 2007). 

---