Interleukin lymphokine-activated killer cell

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. 

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. 

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Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985 313 1485-92. 

Bar MH, Snzol M, Atkins MB, et al. Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine activated killer cells. J Clin Oncol 1990 8 1138-47. 

Denicoff KD, Rubinow DR, Papa MZ, Simpson C, Seipp CA, Lotze MT, Chang AE, Rosenstein D, Rosenberg SA. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1987 107(3) 293-300. 

Law TM, Motzer RJ, Mazumdar M, Sell KW, Walther PJ, O Connell M, Khan A, Vlamis V, Vogelzang NJ, Bajorin DF. Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer 1995 76(5) 824-32. 

Kung AW, Lai CL, Wong KL, Tam CF. Thyroid functions in patients treated with interleukin-2 and lymphokine-activated killer cells. Q J Med 1992 82(297) 33 2. 

Marcus SL, Dutcher JP, Paietta E, Ciobanu N, Strauman J, Wiernik PH, Hutner SH, Frank O, Baker H. Severe hypo-vitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. Cancer Res 1987 47(15) 4208-12. 

Feinfeld DA, D Agati V, Dutcher JP, Werfel SB, Lynn RI, Wiernik PH. Interstitial nephritis in a patient receiving adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells. Am J Nephrol 1991 ll(6) 489-92. 

Rozenberg SA, Lotze MT et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and Interleukine 2 or high dose interleukine 2alone. N ehg J Med. 1987,316,889-897. 

Thompson JA, Shulman KL, Benyunes MC, Lindgren CG, Collins C, Lange PH, Bush WH Jr, Benz LA, Fefer A. Prolonged continuous intravenous infusion interleukin-2 and lymphokine activated killer cell therapy for metastatic renal cell carcinoma. J Clin Oncol 1992,10 960-968. 

Schomburg A, Kirchner H, Atzpodien J Renal, metabolic, and hemodynamic side-effects of interleukin-2 and/or interferon alpha evidence of a risk/benefit advantage of subcutaneous therapy, J Cancer Res Clin Oncol 1993,119 745-755 Margolin KA, Rayner AA, Hawkins MJ, Atkins MB, Dutcher JP, Fisher Rl, Weiss GR, Doroshow JH, Jaffe HS, Roper M, et al. Inter-leukin-2 and lymphokine-activated killer cell therapy of solid tumors analysis of toxicity and management guidelines, J Clin Oncol 1989,7 486-498... 

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... 

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). 

Interleukin-2 Enhances production of T-cells and gamma interferon. Activates natural killer and lymphokine activated killer cells. Under investigation for effectiveness against AIDS, neoplasms, and viral diseases. Hypotension, fever, chills, rigor. 

Boiardi A, Silvani A, Ruffini PA, Rivoltini L, Parmiani G, Broggi G et al. Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients. Cancer Immunol Immunolher 1994 39 193-197. 

Jacobs SK, Wilson DJ, Komblith PL, Grimm EA. Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma phase I trial. Cancer Res 1986 46 2101-2104. 

Merchant RE, Grant AJ, Merchant LH, Young HF. Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer 1988 62 665-671. 

Hayes RL, Koslow M, Hiesiger EM, Hymes KB, Hochster HS, Moore EJ et al. Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 1995 76 840-852. 

Rosenberg SA, Lotze MT, Yang JC et al. (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85 622- 632... 

Roth MD, Pinto M, Golub SH, Shau H. Pulmonary surfactant inhibits interleukin-2-induced proliferation and generation of lymphokine-activated killer cells. Am J Respir Cell Mol Biol 1993 9 652-658. 

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