S. Mandruzzato et al., ADOPTIVE TRANSFER OF LYMPHOKINE-ACTIVATED KILLER-CELLS LOADED WITH 4'-DEOXY-4'-IODODOXORUBICIN - THERAPEUTIC EFFECT IN MICE BEARING LUNG METASTASES, Cancer research, 54(4), 1994, pp. 1016-1020
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.