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Skip to 0 minutes and 14 seconds Now we are going to turn to the bad aspect of immunity. or the bad aspects of the immune response. The immunogenic response of biologics. As I mentioned earlier, immunogenicity is generally undesirable for biologics. Why does it happen? It happens as a defense mechanism, so patient can develop antibody response against the biologics. And the purpose is to be able to get rid of it. because the antigens or the biologics could be completely foreign. For example, insulin derived from porcine or the bovine, or the oligonucleotide which appears almost like a small molecule.

Skip to 1 minute and 11 seconds The antigen may not be completely foreign to the patient but for the innate patient, the clotting factors or growth hormones which are derived from the cadavers, they still are foreign to the innate deficient patient. Because these patients do not have it of this clotting factors or growth hormones to begin with. And the third type of immunogenic response, the Anaohylactic response on re-challenge. For example, the MMR vaccine. If the patient is re-challenged, then it may develop an immediate antigen antibody response that created or resulted in shock. And that’s why travelers sometimes carry a passport warning not to re-vaccinated or a piece of paper to that effect.

Skip to 2 minutes and 21 seconds And fortunately, antigens or biologics are made less foreign by the recombinant DNA technology, although we are not able to completely get rid of it yet. So let’s talk about factors that would affect immunogenicity. First is the source, the origin of the biologics. The structure, chemical structure of the biologics; the impurity that contained in the biologics; the formulation factor, how it’s formulated; the manufacturing process, how the product is processed. For example the freeze drying cycle. Storage condition, temperature, humidity, or even pressure. Those in fact, for example, the route of drug administration that those given and whether concomitant medication is given. Heredity. Some individuals respond very strongly to give an antigen. Others just respond quickly.

Skip to 3 minutes and 37 seconds And some others, lucky one, they don’t respond at all, which is gonna hard to predict. Let’s talk about them one by one. The source, for example, the monoclonal antibodies are derived from the mice. The mice is foreign to human.

Skip to 4 minutes and 2 seconds So patient develop antibody response against the foreign monoclonal antibody. So as to quickly clear it from the system. Give you a couple example. Interference beta produced in E.coli is more immunogenic than that produced in mammalian cells. Why? Because mammalian cells are close to humans than E. coli. For example, dogs treated even it was human epoetin developed immunogenicity Why is that? Because human is foreign to the dogs. Now, epoetin using polysorbate 80 as a surfactant is more energetic than using human serum albumin. Why is that? It is because human serum albumin is closer to human then polysorbate 80. So source, is a factor for immunogenicity.

Immunogenic Response

Biological agents are structurally immunogenic, and therefore usually elicit a minor, subclinical and transient response. Occasionally, however, these biologics induce complete cellular and humoral immune responses, with main clinical consequences being hypersensitivity reactions or loss of treatment response. Integrating immunogenicity information and therapeutic monitoring is important to guide therapeutic decisions in clinical practice.

Factors that influence immunogenicity of biologics are presented. Product related factors include Source (Origin), Structure, Impurity, Formulation, Manufacturing process, Storage condition Patient related factors include Dosing factor (dose, frequency, route), Heredity Epoetin and interferon, two clinical products are used to illustrate the predominant role of origin in immunogenicity

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Pharmacotherapy: Understanding Biotechnology Products

Taipei Medical University