Lymphokine-activated killer cell therapy

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... 

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. 

FIGURE 51.2 Cell transfer therapy with lymphokine-activated killer cells. 

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). 

IL-2 is not directly cytotoxic to cancer cells rather, it induces and expands a T-cell response that is cytolytic for tumor cells. CUnical trials have studied the antitumor activity of IL-2 both as a single agent and with adoptive ceUular therapy using IL-2-stimulated autologous lymphocytes obtained by leukopheresis, termed lymphokine-activated killer (LAK) cells addition of LAK cells to the treatment regimen has not improved overall response rates. 

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