Interferons human

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. 

Buckwold VE, Wei J, Huang Z, Huang C, Nalca A, Wells J, Russell J, Collins B, Ptak R, Lang W, Scribner C, Blanchett D, Alessi T, Langecker P (2007) Antiviral activity of CHO-SS cell-derived human omega interferon and other human interferons against HCV RNA repUcons and... 

Rosina E, Pintus C, Meschievitz C, Rizzedo M (1991) A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis a multicenter Italian study. Hepatology 13 1052-1056... 

Potentially, interferon is an ideal anhviral agent in that it acts on many different vimses and is not toxic to host cells. However, the exploitation of this agent in the treatment of viral infechons has been delayed by a number of factors. For example, it has proved to be species-specific and interferons raised in animal sources offered little protechon to human cells. Human interferon is thus needed for the treatment of human infechons and the produehon and purificahon of human interferon on a large scale has proved difficult. The inserhon of human genes for interferon into E. coli has resolved the produehon problems (Chapter 24). Clinical trials have demonstrated that interferon prevents rhinovirus infeehon and has a beneficial effect in herpes, cytomegalovims and hepahtis B vims infechons. 

Geras-Raaka E, Varma A, Ho H, Clark-Lewis I, Gershengom MC. Human interferon-gamma-inducible protein 10 (IP-10) inhibits constitutive signaling of Kaposi s sarcoma-associated herpesvirus G protein-coupled receptor. J Exp Med 1998 188(2) 405 108. 

Human interferon (hIF-a2b and hIF-a8) CaMV 35S promoter/ nos terminator Native LP ofhIF-a2b andhIF-a8 resp. S. tuberosum 560 IU g 1 tissue 54... 

Virtually all therapeutic glycoproteins, even when produced naturally in the body, exhibit such heterogeneity for example, two species of human interferon-y (IFN-y), one of molecular mass 20 kDa and the other of 25 kDa, differ from each other only in the degree and sites of (N-linked)... 

Table 8.4 Human interferons and the cells that produce them...

Bekisz, J., Schmeisser, H., Hernandez, J., Goldman, N.D., and Zoon, K.C. 2004. Human interferons alpha, beta and omega. Growth Factors 22(4), 243-251. 

Jaffe, H.S. and Herberman, R.B., Rationale for recombinant human interferon-gamma adjuvant immunotherapy for cancer, J Natl. Cancer Inst., 80, 616, 1988. 

Examples of the early application of recombinant DNA technology in medicine are the development of recombinant human growth hormone human insulin human interferons, thought to have anticancer activity in addition to antiviral activity interleukins (regulatory proteins from lymphocytes that are believed to be important in the treatment of immunodeficiency diseases and cancer) tumor necrosis factor epidermal and bone marrow progenitor cell growth factors and the production of vaccines (Table 12.1). 

Stebbing, N. and Week, P.K. (1984). Preclinical assessment of biological properties of recombinant DNA-derived human interferons. In Recombinant DNA Products Insulin, Interferon and Growth Hormone, (Bollon, A.P., Ed.). CRC Press, Boca Raton, FL. 

It should be noted that the unfolding kinetics can sometimes involve quite complex unfolding schemes of different substates in equilibrium with the native state. Staphylococcal nuclease is an example of such behavior, known to unfold with three different substates that exhibit an equilibrium that does not appear to shift with temperature.49 Irreversible aggregation processes of proteins have been known to involve first- or second-order reactions.132141 The mechanism of recombinant human interferon-y aggregation is an example where thermodynamic and kinetic aspects of the reaction provided a powerful tool for understanding the pathway of instability and permitted a rationale for screening excipients that inhibited the process.141... 

Kendrick, B.S., J.F. Carpenter, J.L. Cleland, and T.W. Randolph. 1998. A transient expansion of the native state precedes aggregation of recombinant human interferon-gamma. Proc Natl Acad Sci U.S.A. 95 14142-14146. 

High temperatures can break native S-S bonds and form new S-S bonds which can lock the protein into a denatured eonfiguration [89]. Low pH, sodium dodecyl sulfate. Tween 80, chaotropie salts, and exogenous proteins have been used to protect proteins from thermal inaetivation [90]. Ethylene glycol at 30-50% was used to protect the antiviral activity of P-interferon preparations [91]. Human serum albumin was used in recombinant human interferon-Psei-n which resulted in increased thermal stability [62]. Water-soluble polysaeeharides sueh as dextrans and amylose [92], as well as point-specific (site-directed) mutagenesis [93] have also been used to increase thermal stability of therapeutie proteins and peptides. 

The cell culture supernatants from PBMCs stimulated with DIMS were analyzed by ELISA for the presence of human interferon a and P (IFNa and IFNP). 

T Yu, Y Xiao, Y Bai, Q Ru, G Luo, MP Dierich, YH Chen. Human interferon-beta inhibits binding of HIV-1 gp41 to lymphocyte and monocyte cells and binds the potential receptor protein P50 for HIV-1 gp41. Immunol Lett 73 19-22, 2000. 

Interferons are natural proteins produced by the cells of the immune system in response to challenges by foreign agents such as viruses, parasites and tumor cells. Interferons assist the immune response by inhibiting viral replication within host cells. There are three major classes of interferons, interferon type I, interferon type II and interferon type III. They bind to a differen cell surface receptor complexes. The type I interferons in humans are IFN-o , IFN-jS and IFN- >. IFN-y is human interferon type II. All classes of interferon are important in fighting RNA virus infections and endogenous interferons are secreted when abnormally large amounts of dsRNA are found in a cell. 

ITABLE 7.3. Commercially available preparations of human interferon... 

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