Fractionated extract of Astragalus membranaceus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2.
Success with rIL-2 immunotherapy of human cancer appears to depend on the administration of high doses which are frequently associated with excessive toxicity. Future use of rIL-2 will require certain modifications based on the use of lower doses of rIL-2 without significant loss of antitumor efficacy. We tested in vitro the possibility of potentiating the activity of rIL-2 in terms of LAK cell generation. We hypothesized that co-incubation of LAK cell precursors with a Chinese herbal extract (F3) of Astragalus membranaceus, (an immune modulator currently under study in our laboratory), along with a low concentration of rIL-2, would generate levels of LAK cell activity equivalent to those generated by high concentrations of rIL-2 alone. We found (1) a 10-fold potentiation of rIL-2 activity manifested by tumor cell-killing activity of 80% resulting from LAK cell generation with F3 plus 100 u/ml of rIL-2 versus 76% generated by 1,000 u/ml of rIL-2 alone; (2) a significant reduction in the number of effector LAK cells required for equicytotoxic reaction following LAK cell generation with F3 plus rIL-2 compared to rIL-2 alone. We conclude that potentiation of antitumor activity mediated by rIL-2 in low concentrations is possible by the concomitant use of another immune modulator such as Astragalus membranaceus.
Chu
D T
DT
Department of Clinical Immunology and Biological Therapy, University of Texas System Cancer Center, Houston 77030.
Lepe-Zuniga
J
J
Wong
W L
WL
LaPushin
R
R
Mavligit
G M
GM
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology*; D027885:Astragalus propinquus; D002460:Cell Line; D005591:Chemical Fractionation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008545:Melanoma / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D004365:Drugs, Chinese Herbal; D007376:Interleukin-2; D011994:Recombinant Proteins