Interferon lymphoblastoid

Interferon-a. Alfa-interferon alpha-interferon IFN- LelF leukocyte interferon lymphoblastoid interferon. Family of highly homologous species -specific proteins that inhibits viral replication and cellular proliferation and modulates the immune response. One of the type I interferons. Produced by peripheral blood leukocytes or lymphoblastoid cells upon exposure to live or inactivated virus, double-stranded RNA. Or bacterial products. Multiple sub-types have been identified which contain 163-166 amino acids mol wt approximately 18.000-20,000 daltons. Production by virus stimulated human leukocytes I. Gresser, Proc. Soc. Exp. Biol Med. 108, 799 (1961). Purification C. 

Cancer now afflicts one out of four adults. One of the more promising therapies for certain kinds of cancers involves the use of interferon, a protein that occurs in minute quantities in the body where it is an essential part of the body s immune system. Interferon can be produced outside the body in cultures of transformed lymphoblastoid cells. A few years ago, it was possible to culture these human cells on scales up to a few hundred milliliters. Chemical engineers have now developed reactors for the aseptic culture of human cells on a scale 100,000 times larger, making it possible to produce human interferon in practical useful quantities. 

Pastore G, Santantonio T, Milella M, Monno L, Mariano N, Moschetta R, PolUce L (1992) Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon. J Hepatol 14 221-225 Pawlotsky JM (2006) Therapy of hepatitis C from empiricism to eradication. Hepatology 43 S207-S220... 

PhUlpotts RJ, Higgins PG, WUlman JS, Tyrrell DA, Freestone DS, Shepherd WM (1984) Intranasal lymphoblastoid interferon ( WeUferon ) prophylaxis against rhinovirus and influenza virus in volunteers. J Interferon Res 4 535-541... 

In addition to recombinant biopharmaceuticals, animal cell culture is used to produce various other biologically based pharmaceuticals. Chief amongst these are a variety of vaccines and hy-bridoma cell-produced monoclonal antibodies (Chapter 13). Earlier interferon preparations were also produced in culture by a particular lymphoblastoid cell line (the Namalwa cell line), which was found to synthesize high levels of several IFN-a s naturally (Chapter 8). 

Hannigan, G.E., D.R. Gewert, E.N. Pish, S.E. Read, and B.R. Williams, Differential binding of human interferon-alpha sub-types to receptors on lymphoblastoid cells. Biochem Biophys Res Commun, 1983. 110(2) 537 4. 

Ruzicka, F.J., M.E. Jach, and E.C. Borden, Binding of recombinant-produced interferon beta ser to human lymphoblastoid cells. Evidence for two binding domains. J Biol Chem, 1987. 262(33) 16142-9. 

Interferons and cytokines Interferon alfa-nl, Lymphoblastoid (natural product) Wellferon 3MU in 1ml IM,SC... 

Interferons (IFN) are glycoproteins which possess antiviral, antiproliferative and immunomodulatory properties. Besides the main types a, P and y, other forms are available (lymphoblastoid IFNa, consensus IFNa). Administration is subcutaneous. Bioavailability is about 90%. The serum peak is reached by using IFNa2a after 6-8 hours with a half-life period of 5 hours or by using IFNa2b after 3-12 hours with a half-life of 3 hours. Elimination is primarily via the kidneys. Interferons inhibit CYPIA2. There is no development of resistance. (158, 160, 182) (see chapter 40.5.1.1)... 

Interferon alfa is used as purified natural leukocyte or lymphoblastoid human interferon, or as a recombinant DNA preparation. Work to assign the most frequently observed amino acids at each position has led to a so-called consensus interferon alfa (1). Relatively low doses (3-10 MU three times a week) are now being used in most indications, except in AIDS-related Kaposi s sarcoma (up to 30 MU/day). Although the half-life is only 4-5 hours, its biological effects persist for 2-3 days. 

Although the adverse effects profiles of the currently available formulations of interferon alfa are very similar, patients who have adverse effects with one formulation can be successfully re-treated with another type of interferon alfa. This has been shown in 22 patients in whom lymphoblastoid interferon alfa was withdrawn because of severe adverse effects (leukopenia, thrombocytopenia, thyroid disorders, and psychiatric disturbances) and were successfully re-treated with similar dosages of leukocyte interferon alfa (22). Only one of these patients had severe leukopenia again. 

Mirro J Jr, Kalwmsky D, Whisuaut J, Week P, Chesney C, Murphy S. Coagulopathy iuduced by continuous infusion of high doses of human lymphoblastoid interferon. Cancer Treat Rep 1985 69(3) 315-17. 

Krogsgaard K, Marcellin P, Trepo C, Berthelot P, Sanchez-Tapias JM, Bassendine M, Tran A, Ouzan D, Ring-Larsen H, Lindberg J, Enriquez J, Benhamou JP, Bindslev N. Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group. J Hepatol 1996 25(6) 803-13. 

Russo D, Candoni A, Zuffa E, Minisini R, Silvestri F, Fanin R, Zaja F, Marline Hi G, Tura S, Botta G, Baccarani M. Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph-f chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha. Br J Haematol 1996 94(2) 300-5. 

Mirro J, Dow LW, Kalwinsky DK, Dahl GV, Week P, Whisnant J, Murphy SB. Phase 1-11 study of continuous-infusion high-dose human lymphoblastoid interferon and... 

Baker PN, Morser J Burke DC (1980) Effects of sodium butyrate on a human lymphoblastoid cell line (Namalwa) and its interferon production. Journal of Interferon Research 1 (1) 71-77. 

Johnston MD (1980) Enhanced production of interferon from human lymphoblastoid (Namalwa) cells pre-treated with sodium butyrate. Journal of General Virology 50 191-194. 

Large scale production of human lymphoblastoid (Namalva) interferon. 1. Production of crude interferon. Biotechnology Letters 2 (6) 267-271. 

Italy interferon alfa interferon Alfaferone Oif Veldona Natural human lymphoblastoid alpha interferon Hepatitis... 

Various regimens of interferon-a have been attempted (197) and it has been found that longterm (> 1 month) low-dose therapy was more effective and better tolerated than short-term high-dose therapy (195, 198). Similar results were obtained with recombinant and lymphoblastoid preparations (199-201). The success rate was 30-40%, as judged by decreases in serum viral DNA, and patients responding to therapy have shown losses of HBeAg as well as decreased serum aminotransferase levels. Follow-up liver biopsies demonstrate reduced inflammation (198). It is hoped that this reduces the risk of subsequent cirrhosis and carcinoma which is a time-dependent process. Several studies have been performed to evaluate restoration of hepatic markers during and after interferon-a treatment, simply or in combination with other therapies to treat chronic hepatitis B (see section 6.3.5 below). 

Priestman T J, Johnston M, Whiteman P D (1982). Peameability observations on the pharmacokinetics of human lymphoblastoid interferon given by intramuscular injection. Clin. Oncol. 8 265-269. 

Burysek L, Pitha PM (2001) Latently expressed human herpesvirus 8-encoded interferon regulatory faetor 2 inhibits double-stranded RNA-aetivated protein kinase. J Virol 75 2345-2352 Cahir-MeFarland ED, Davidson DM, Sehauer SL, Duong J, Kieff E (2000) NF-kappa B inhibition causes spontaneous apoptosis in Epstein-Barr virus-transformed lymphoblastoid cells. Proc Natl Acad Sci USA 97 6055-6060... 

Johnston MD, Christofinis G, Ball GD, Fantes KH, Pinter NB. (1979) A culture system for producing large amounts of human lymphoblastoid interferon. Dev. Biol. Stand. 

In view of these data, it seems quite probable that the decrease of ADPRT activity found in L cells, especially in nuclei, can be explained as a consequence of enzyme inhibition by increased amounts of oligoadenylates following interferon treatment. The observation that glucocorticoid administration to lymphoblastoid cells increases the level of 2, 5 A polymerase activity drastically [16], and that glucocorticoids enhance the expression of the prolactin gene in pituitary glands with concomitant decrease of ADP-ribosylation of nuclear nonhistone proteins HMG 14 and 17 [17], support our interpretation. 

Figure 1.8 Continuous-flow Z41 CEPA centrifuge installed in a glove box for the separation of Namalva cells from supernatant in the mass produc-ticn of lymphoblastoid interferon. (Courtesy of New Brunswick Scientific Co., Inc.)...

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