Interleukin therapy study

Parker, S. E., Khatibi, S., Margalith, M., Anderson, D., Yankauckas, M Gromkowski, S. H., Latimer, T Lew, D., Marquet M Manthorpe M., Hobart, P., Hersh, E., Stopeck, A. T and Norman, J. (1996) Plasmid DNA gene therapy studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo. Cancer Gene Ther. 3(3), 175-185. 

H6. Hack, C. E., Ogilvie, A. C., Eisele, B., Jansen, P. M Wagstaff, J., and Thijs, L. G Initial studies on the administration of Cl-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. Prog. Clin. Biol. Res. 388, 335-357 (1994). 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

Recent studies showed that rituximab down-regulates interleukin-10 (lL-10) in some lymphoma cell lines (17,18,19,20,21,22,23,24,25,26,27). IL-10 has a stimulatory function as an autocrine or paracrine growth factor for lymphoma cells (28). lL-10 is a known promoter of BCL2 expression in hematopoietic cells (29) as well as lymphoma cells (28). Rituximab is known to induce down-regulation of lL-10 expression and consequently of bcl-2 protein expression, making B-cells more susceptible to apoptotic signals (Fig. 1) (30,31,32). However, the implication of lL-10 on clinical outcome after rituximab therapy is still unclear. 

This is not to say that cardiotoxicity is not seen with biopharmaceuticals. Cardiomyopathy is now a well-recognized complication of trastuzumab and and has been reported with bevacizumab treatment, in particular in combination with other cytotoxic cancer therapies [20]. Myocarditis and pericarditis are a well-documented complications of vaccinia immunization [21], and could also complicate use of a pox-virus vector for other therapeutics. In 1995 Genetics Institute suspended phase 2 cancer trials of Interleukin-12 for serious tox-icities including cardiac arrhythmia. However, such toxicities are best detected by incorporation of biomarkers for myocardial damage such as troponin-T into preclinical and early clinical studies, and continual ECG monitoring for arrhythmia in preclinical and early clinical studies, not by in vitro explorations of electrophysiology. 

The promising second oral therapy is Temsirolimus (Wyeth Pharm). Temsirolimus is believed to block the proliferation of immune T cells activated by interleukin, IL-2. The phase It clinical trial of Temsirolimus was also an international double blind placebo controlled trial. The trial involved 296 patients with either RR MS or SP MS with relapses. Participants received one of three doses of oral temsirolimus or placebo daily for 9 months. The primary outcome measure was the number of enhancing lesions after 9 months in study. By 32 w eeks into the study, those in the highest treatment dose had 47.8% fewer new enhancing lesions compared to those on placebo. The high dose group also had 51 % fev er relapses than the placebo group. Side effects included mouth ulceration or inflammation, menstrual dysfunction, hyperlipidemia and rashes. 

Multigene studies have shown that interleukin (IL)-1 3 genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-week triple therapy for H. pylori infections. ... 

In some cases, cell surface expression of certain species can be induced for example, interleukin-1 has been shown to induce the biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells [197]. Such materials may also be exploitable as candidates for bioadhesion studies. Millions of lives of patients with diabetes have been saved since the introduction of insulin therapy. However, several daily injections of insulin are required to maximize glucose control in diabetic patients. Insulin is administered by subcutaneous injection, but this route of administration has a slow onset and subsequent prolonged duration of action. These limitations show up more when higher doses of insulin are injected, which results in a long duration of action and forces the patients to consume additional amounts of food to limit the risk of hypoglycemia [198]. 

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