ADOPTIVE TRANSFER OF LYMPHOKINE-ACTIVATED KILLER-CELLS LOADED WITH 4'-DEOXY-4'-IODODOXORUBICIN - THERAPEUTIC EFFECT IN MICE BEARING LUNG METASTASES

We studied the potential use of lymphokine-activated killer (W() cells loaded with 4'-deoxy-4'-iododoxorubicin (IDX) in adoptive immuno-ther apy experiments. Because LAK cells preferentially locate in the lung, me evaluated the therapeutic effect of IDX-loaded Wt cells in mice bea ring lung metastases induced by B16F1 tumor cell injection. In vitro s tudies shelved that Wt cells rapidly incorporated IDX, with maximum up take at 15 min, followed by a plateau; drug efflux was initially rapid and then continued at a much slower rate. Evaluation of Wt cell cytot oxic activity against relevant target cells showed a 30% decrease afte r IDX treatment that progressed with time over the next 6 h. P388 tumo r cell growth was inhibited by coculture with IDX-loaded Wt cells, thu s demonstrating that the released IDX maintained its pharmacological a ctivity. Finally, high performance liquid chromatography analysis of t issue IDX concentration revealed a considerably higher and long-lastin g concentration in the lungs of mice receiving IDX-loaded Wt cells, co mpared to mice given injections of a comparable amount of free drug. M oreover, adoptive transfer of IDX-loaded Wt cells into tumor-bearing m ice caused a significant reduction in the number of lung metastases ve rsus control mice given injections of even higher doses of free drug.