Potentiatied antitumor effectiveness of combined chemo-immunotherapy with Interleukin-12 and 5-fluorouracil of L1210 leukemia in vivo

Abstract

In this study we investigated the efficacy of a combination of IL-12 and 5-FU, a chemotherapeutic exerting several immunomodulatory effects, in murine L1210 leukemia. Mice inoculated with 1 × 105 leukemia cells were treated with a single dose of 5-FU (50 mg/kg) and seven daily doses of IL-12 (100 ng/dose), and were observed for survival. Treatment with IL-12 or 5-FU given alone produced moderate anti-leukemic effects. However, combination of both drugs resulted in a significant prolongation of mouse survival time. Importantly, there were 70% of long-term (>60 days) survivors among mice treated with both agents simultaneously. Moreover, we observed 100% of long-term survivors when mice were treated with a minimally increased dose of IL-12 (170 ng) in combination with 5-FU (50 mg/kg). The antileukemic effects were completely abrogated in scid/scid mice and in mice depleted of peritoneal macrophages and significantly decreased after administration of anti-CD3+, anti-CD4+ or anti-CD8+ monoclonal antibodies. Administration of anti-NK1.1 antibodies did not decrease the antileukemic effects indicating that NK cells are not important effectors of this treatment regimen. Collectively, these results indicate that the combination of IL-12 and 5-FU is inducing strong antileukemic responses that are dependent on the presence and activity of macrophages and T lymphocytes and warrant further studies of combined chemo-immunotherapy with IL-12.

DOI: 10.1038/sj.leu.2402076
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@article{Gob2001PotentiatiedAE, title={Potentiatied antitumor effectiveness of combined chemo-immunotherapy with Interleukin-12 and 5-fluorouracil of L1210 leukemia in vivo}, author={J Gołb and Radoslaw Zagozdzon and Rafal Kamiński and Katarzyna Kozar and Katarzyna Gryska and Dariusz M Izycki and Andrzej Mackiewicz and Tomasz Stokłosa and Adam S. Giermasz and Witold Lasek and Marek Jak{\'o}bisiak}, journal={Leukemia}, year={2001}, volume={15}, pages={613-620} }