TY - JOUR
T1 - Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations
AU - Hank, Jacquelyn A.
AU - Surfus, Jean
AU - Gan, Jacek
AU - Albertini, Mark
AU - Lindstrom, Mary
AU - Schiller, Joan H.
AU - Hotton, Kirsten M.
AU - Khorsand, Masoud
AU - Sondel, Paul M.
PY - 1999/2
Y1 - 1999/2
N2 - 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 !L-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 α into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 106 IU of HLR IL-2 than were seen in patients treated with 1.5 x 106 or even 4.5 x 106 IU of Chiron/L-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using !L-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 ~3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.
AB - 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 !L-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 α into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 106 IU of HLR IL-2 than were seen in patients treated with 1.5 x 106 or even 4.5 x 106 IU of Chiron/L-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using !L-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 ~3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.
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M3 - Article
C2 - 10037176
AN - SCOPUS:0033011520
SN - 1078-0432
VL - 5
SP - 281
EP - 289
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -