Purification and characterization of recombinant human interleukin-2 produced in Escherichia coli

Kato, Koichi; Yamada, Takao; Kawahara, Kenji; Onda, Haruo; Asano, Tsuneo; Sugino, Hiromu; Kakinuma, Atsushi

doi:10.1016/0006-291x(85)90472-3

Cited by 104 publications

(27 citation statements)

References 14 publications

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“…The specific activity of radiolabeled IL-2 was determined by correlating radioactivity with biologic activity (18). Biologic activity and protein mass were determined on homogeneous, IL-2, kindly supplied by Dr. K. Kato, Takeda Chemical Industries, Ltd., Osaka, Japan (19). Using this preparation as a standard, previous calculations (16) of protein concentration and biologic activity were found to overestimated fourfold.…”

Section: Methodsmentioning

confidence: 99%

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Gullberg¹,

Smith²

1986

The Journal of Experimental Medicine

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During the course of investigating the regulation of IL-2-dependent T cell proliferation, we found that the subset of human T cells expressing the T4 surface glycoprotein become refractory to IL-2 growth promotion earlier than T8+ cells. Since T4+ cells proliferate in an autocrine fashion to endogenous IL-2, whereas most T8+ cells respond in a paracrine fashion to IL-2 derived from T4+ cells, we thought it likely that a unique mechanism was operative to restrict T4+ cell IL-2-dependent autocrine proliferation. Moreover, we anticipated that the T4+ cell IL-2-refractory state related either to suppression by T8+ cells, or to expression of T4+ cell IL-2-R. However, several experimental approaches did not support either of these mechanisms as being responsible for the loss of T4+ cell IL-2 responsiveness. Isolated T4+ cells ceased to respond to IL-2 well before T8+ cells, and before the disappearance of adequate levels of IL-2-R. Moreover, a detailed comparison of IL-2-R expression by T4+ vs. T8+ cells revealed no differences in the number, affinity, rate of expression, or functional activity of high-affinity IL-2-R expressed by the two subsets. Accordingly, T4+ cell autocrine IL-2 responsiveness is restricted by a mechanism that is independent of IL-2-R, and which ultimately results in cessation of both T4+ and T8+ cell IL-2-dependent clonal expansion.

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Section: Methodsmentioning

confidence: 99%

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Gullberg¹,

Smith²

1986

The Journal of Experimental Medicine

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“…MD), Human recombinani IL-2 (rIL-2) was kindly provided by Takeda Pharmaceutical Co, (Osaka. Japan), anil bad a specific activity of 3 5 x KH U/mg as assayed on IL-2-dependent murine NKC3 cells [21]. Human rlL-6 (lot 735-3: specific activity 6x10'' U/mg of protein) was a gift from Ajinomoto Co. (Kawasaki.…”

Section: Sulyjectsmentioning

confidence: 99%

IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2

Yanagawa

Sone

Munekata

et al. 1992

Clinical and Experimental Immunology

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SUMMARYThe levels and activities of endogenous IL-6 in malignant pleura! effusions due to lung cancer before and during daily intrapleural instillations of reeombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependenl murine hybridoma cell line MH60.BSF2. Before therapy, malignant pieural effusions contained various levels of IL-6. Daily intrapteural instillation of recombinani lL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleura! effusions. On fractionation of the pieural effusion by chromatography. one major peak ofmateria! with a mo!, wi of 24 k D showed lL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-I/J was delectable in pieural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 producUoti.

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“…r[L-2 was extracted from Escherichia coli transfected with a plasmid containing human IL-2-encoding cDNA. The purification and biochemical characterization of the rIL-2 preparation (TGP-3) was detailed elsewhere [12,13]. Anti-rlL-2 monoclonaI antibody.…”

Section: Methodsmentioning

confidence: 99%

Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2

et al. 1993

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We have investigated biological properties of an immune complex of recombinant interleukin-2 (rIL-2) and a monoclonal antibody against rIL-2 in mice for induction of killer cells and for anti-tumor activity. We have also examined the clearance of subcutaneously-injected immune complex in mice and compared it with that of rIL-2 alone. Plasma rIL-2 levels were sustained longer in mice given the immune complex than in mice given rIL-2 alone at a dose of 10 micrograms/mouse, and they were detectable even at 24 hours after the administration of the immune complex, while they fell to undetectable levels by 6 hours after the administration of rIL-2 alone. A more significant portion of rIL-2 was detected in lymph nodes after subcutaneous injection of the immune complex than that of rIL-2 alone. Splenic lymphocytes from mice given the immune complex demonstrated a higher killer cell activity against YAC-1 cells than those from mice given rIL-2 alone. The immune complex also exerted more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than rIL-2 alone. Our results indicate that immunocomplexing of rIL-2 with an antibody against rIL-2 provides a useful tool as the drug delivery system for cancer therapy using rIL-2.

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Purification and characterization of recombinant human interleukin-2 produced in Escherichia coli

Cited by 104 publications

References 14 publications

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2

Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2

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