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• W802831775 abstract "The effectiveness of adoptive immunotherapy of cancer using LAK cellsand IL-2 depends on the accumulation of transferred effector cells at thetumour sites. In vitro LAK cell have been demonstrated to have broadcytotoxic activity to a wide variety of tumour cells in a non-major-histocompatibilitycomplex-restricted manner, and independent of thepresence of tumour specific antigens. LAK cells have now been usedeffectively in a small number of human trials. The effective delivery ofthese cells to the tumour site in vivo is one of the main aspects of this typeof immunotherapy that requires further investigation. Conventionalsystemic infusion has shown a limited migration pattern of LAK cells. Inthis study the degree of entrapment of LAK cells in organs following localinfusion has been determined. The large size and rigidity of LAK cellsmay be one mechanism which restricts the distribution of these cells. Inaddition, in this study the effect of mannitol, a hyperosmotic agent whichincreases the space between vascular endothelial cells, on the uptake ofintraportal LAK cells into liver has been determined.A-LAK cells are obtained by culture of N.W.P. lymphocytes with IL-2. Inthis study A-LAK cells were characterised by typical morphologicappearance, cell surface phenotype, and cytotoxic specificity. Purified A-LAKcells were morphologically large granular lymphocytes, 67%-90% ofwhich showed the surface marker phenotype of NK/LGL cells (OX8). Thepopulation contained few pan-T cells (only 4.0-6.5% of cells expressingOX19). No B cell surface marker lg was detectable in the A-LAK cellpopulation. These cells showed high ability to lyse YAC-1 and P-815cultured tumour target cells in 4h 51Cr-release cytotoxic assays. At an Effector:Target ratio of 40:1 A-LAK cells lysed 70% P815 and 100% YAC-1cells.After labelling A-LAK cells with 51Cr, the effect of intraportal infussion of30% mannitol on the distribution of intraportally infused A-LAK cells inliver was studied. The trafficking studies were carried out in threegroups. In Group 1, 51Cr labelled A-LAK cells were systemically infusedthrough the tail vein of rats as a control group. In Group 2 and Group 3,A-LAK cells were infused into syngeneic rats through the portal veinwithout or following prior portal infusion of 30% mannitol. Two hoursafter LAK cell administration the rats were sacrificed and the radioactivityin liver, lung, spleen, blood, MLN, kidney and brain were measured todetermine the distribution of A-LAK cells to these organs.The results showed that intraportal mannitol was associated with anincreased percentage of LAK cells in the liver compared with regionallyinfused LAK cells without mannitol (54% vs 24%; P<0.0005). Theadministration of intraportal mannitol was also associated with increaseddistribution of A-LAK cells into the brain (0.26% vs 0.08%; P<0.05) andMLN (0.05% vs 0.02%; P<0.05). There was no significant increase inuptake of A-LAK cells in lung (8.39% vs 6.01 %), spleen (1.00% vs 0.98%),or kidney (1.44% vs 1.78%) following intraportal mannitol.There was no significant increase of the A-LAK cell distribution to theliver by regional infusion without mannitol (24% vs 16%). Systemicinjection gave greater A-LAK uptake into lungs (15.65%) than portalinjection (6.05%, P=0.05). There was no significant differences of celldistribution in spleen, MLN, kidney and brain by these two routes ofinfusion. These results showed that mannitol has the effect of increasing thedistribution of LAK cells into the liver. Augmentation of LAK cellaccumulation in the liver may help to enhance the tumouricidal activity ofthese cells to hepatic metastases. The results of this thesis suggest area_s forfurther investigation into the effect of mannitol and other agents on A-LAKcell uptake into the liver following regional infusion." @default.
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• W802831775 date "1994-01-01" @default.
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• W802831775 title "The effect of intraportal mannitol on the short-term in vivo distribution of radiolabelled A-LAK cells in rats" @default.
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