Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations.
Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer cells, T cells, and other cells of the immune system. Several distinct recombinant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma. Somewhat distinct immune and clinical effects have been noted when different IL-2 preparations have been tested clinically; however, the regimens and doses used were not identical. To compare these more directly, we have evaluated two clinical recombinant IL-2 preparations in vitro and in vivo using similar regimens and similar IUs of IL-2. We used the Food and Drug Administration-approved, commercially available Chiron IL-2 and the Hoffmann LaRoche (HLR) IL-2 supplied by the National Cancer Institute. Using equivalent IUs of IL-2, we noted quantitative differences in vitro and in vivo in the IL-2 activity of these two preparations. In patients receiving comparable IUs of the two preparations, HLR IL-2 induced the release of more soluble IL-2 receptor alpha into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 10(6) IU of HLR IL-2 than were seen in patients treated with 1.5 x 10(6) or even 4.5 x 10(6) IU of Chiron IL-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using IL-2-dependent human and murine cell lines indicated that the IU of HLR IL-2 was more effective than Chiron IL-2 at inducing tritiated thymidine incorporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors. These findings indicate that approximately 3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.
Hank
J A
JA
Department of Human Oncology, Comprehensive Cancer Center, University of Wisconsin, Madison 53792, USA.
Surfus
J
J
Gan
J
J
Albertini
M
M
Lindstrom
M
M
Schiller
J H
JH
Hotton
K M
KM
Khorsand
M
M
Sondel
P M
PM
D000818:Animals; D019002:CD56 Antigen / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007260:Infusion Pumps; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012015:Reference Standards; D012709:Serum Albumin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019002:CD56 Antigen; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D012709:Serum Albumin