Insulin immunogenicity studies

Carcinogenicity used the 12-month repeat dose study instead of a standard 2-year bioassay Other cardiovascular study in dogs drug interaction study with NPH insulin immunogenicity in rabbits In vitro immunology, and Athymic nude mice proof of concept studies... 

Other mitogenicity in CHO-K1 and human BIO osteosarcoma cells, human hepatoma cells and MCF-7 cells to include drug binding study to IGF-1 and insulin receptors local tolerance in pigs immunogenicity studies in rabbits... 

Baker, R. S., Schmidtke, J. R., Ross, J. W., and Smith, W. C. (1981). Preliminary studies on the immunogenicity and amount of Escherichia coli polypeptides in biosynthetic human insulin produced by recombinant DNA technology. Lancet 2(8256), pp. 1139-1142. 

In contrast, different formulations of insulin and growth hormone containing the same active ingredient exhibit significant differences in bioavailability [20]. Additionally, the inability to adequately predict immunogenic responses from in vitro data or animal studies remains a concern. 

The long-term antigenicity of insulin lispro and crossreactivity with human insulin antibodies over 4 years has been investigated in 1221 patients with both type 1 and type 2 diabetes, either insulin-naive or with prior insulin treatment, in a multicenter combination of controlled and non-controlled open studies (30). Like recombinant human insulin, insulin lispro elicited a low immunogenic response. The reversal of amino acids in B28 and B29 is in a relatively non-immunogenic area. Moreover, antigenicity often correlates with residence of insulin in... 

Both pork and human insulin are definitively less immunogenic than beef insulin, producing fewer circulating insulin antibodies, but several studies have indicated no detectable change in antibody concentrations on switching from pork to human insulin or vice versa. Antibodies cause lipoatrophy and are responsible for the substantial insulin resistance seen in some patients, but both events are rare now that purified pork insulin is in common use. Interest has recently been revived in the possible contribution of antibodies in modifying metabolic control. In the short term and under hospital conditions, they are known to prolong the intravenous half-life of injected insulin and to delay the appearance in the circulation of a subcutaneously administered bolus dose. 

Studies in animals, healthy adults, and patients with type I diabetes mellitus have shown human insulin fo have pharmacologic effects identical to those of purified porcine insulin. A comparable pharmacokinetic profile also has been shown. Human insulin, however, administered intramuscularly or intravenously, may have a slightly faster onset and slightly shorter duration of action when compared with purified porcine insulin in patients with diabetes. The usual precautions concerning foxic potentials observed with insulin of animal origin should be followed with rDNA human insulin. As would be expected, the recombinant product has been shown fo be less immunogenic than animal insulins. 

In a recent study, it was found that treatment of diabetic patients by using an implantable pump to dehver insulin into the peritoneal cavity leads to a greater immunogenicity of insulin as compared to conventional therapy (Lassmann-Vagueeta/., 1995). 

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