Gene therapy, cytokines

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

Table 11.6. Some specific cancer types for which human gene therapy triafs have been initiated. Although several of the strategies listed in Table 11.5 are being employed in these trials, many focus upon the introduction of various cytokines into the tumour cells themselves in order to attract and enhance a tumour-specific immune response...

S. Chada, R. Ramesh, A. M. Mhashilkar (2003). Cytokine- and chemokine-based gene therapy for cancer. Curr. Op. Mol. Ther. 5 463 74. 

Nakano, A., A. Matsumori, S. Kawamoto, H. Tahara, E. Yamato, S. Sasayama, and J.I. Miyazaki, Cytokine gene therapy for myocarditis by in vivo electroporation. Hum Gene Ther, 2001.12(10) 1289-97. 

A replication-deficient adenovirus has been used to deliver a gene construct, which contains within its promoter region a radiation-responsive element. Upon irradiation with conventional doses of X rays, this construct initiates transcription of the gene coding for the toxic cytokine, tumor necrosis factor-a (35). The above is an exquisite example of how emerging delivery and gene therapies are fast blurring the distinction between an active and an excipient (Fig. 3D). 

Insulin-dependent diabetes mellitus (IDDM) is an example of a metabolic disease under active consideration for inducible gene therapy strategies. In this disorder, inflammatory cytokines have been shown to activate apoptosis in pancreatic beta cells. Experimental studies indicate that expression of insulinlike growth factor-1 (IGF-1) can prevent the cytokine-mediated destruction of beta cells of the pancreas (Giannoukakis et al., 2001). Regulated expression of IGF-1 in human pancreatic islets, to preserve beta cell function, may be a useful approach in the treatment of certain types of diabetes (Demeterco and Levine, 2001). 

Gautam, A., Densmore, C.L. and Waldrep, J.C. (2001) Pulmonary cytokine responses associated with PEI-DNA aerosol gene therapy. Gene Ther., 8,254-257. 

Rakhmilevich, A.L., Janssen, K., Turner, J., Culp, J. and Yang, N.-S. (1997) Cytokine gene therapy of cancer using gene gun technology Superior antitumor activity of IL-12. Hum. Gene Then, 8, 1303-1311. 

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