Phytochemicals potentiate interleukin-2 generated lymphokine-activated killer cell cytotoxicity against murine renal cell carcinoma

Abstract

The success of adoptive immunotherapy using recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in several cancers has been hampered by severe toxicity associated with high doses of rIL-2. Methods that reduce the dosage of rIL-2 without loss of clinical efficacy are needed. In this study we determined the in vitro effect of a phytochemical immune modulator, Astragalus membranaceus (AM), and two fractions isolated by high-performance liquid chromatography on the cytotoxicity of rIL-2-generated LAK cells against a murine renal cell carcinoma. Our results indicated a 10-fold potentiation of rIL-2-generated LAK cell cytotoxicity manifested by tumor cell lysis of 88% in the group with 100 U/ml of rIL-2 plus AM versus 86% in the group with 1,000 U/ml of rIL-2 alone. Potentiation was obtained with the purified fractions as well. A significantly reduced number of LAK cells was required to achieve the tumor cytotoxicity after LAK cell generation with rIL-2 plus the phytochemicals as compared with rIL-2 alone. Our data indicate that AM is an effective immune modulator, capable of potentiating in vitro the antitumor activity of rIL-2-generated LAK cells.