biology

Olamkicept

Olamkicept is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Olamkicept rather than just read about it. In short: Olamkicept, also known as soluble gp130Fc or sgp130Fc (other designations are FE 999301, FE301, TJ301) is an immunosuppressive drug candidate, which selectively blocks activities of the cytokine Interleukin-6, which are mediated by the soluble Interleukin-6 receptor. Interleukin-6 is a cytokine, which plays a dominant role in the regulation of the immune response and also in autoimmunity.

Key takeaways

Olamkicept belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Olamkicept to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Olamkicept from memory before moving on to harder problems.

Reference excerpt

Olamkicept, also known as soluble gp130Fc or sgp130Fc (other designations are FE 999301, FE301, TJ301) is an immunosuppressive drug candidate, which selectively blocks activities of the cytokine Interleukin-6, which are mediated by the soluble Interleukin-6 receptor. Interleukin-6 is a cytokine, which plays a dominant role in the regulation of the immune response and also in autoimmunity. Furthermore, Interleukin-6 has been demonstrated to be involved in the regulation of metabolism and body weight. Interleukin-6 also has many activities on neural cells. The biochemical principle was invented by the German biochemist Stefan Rose-John and it was further developed into a biotech compound by the Conaris Research Institute AG, which gave an exclusive world-wide license to the Swiss-based biopharmaceutical company Ferring Pharmaceuticals. In December 2016, Ferring and the biotech company I-MAB signed a licensing agreement granting I-MAB exclusive rights in Asia to Olamkicept for the treatment of autoimmune disease.

Mechanism of action On cells, interleukin-6 binds to an Interleukin-6 receptor, which, however, is not signaling. The complex of Interleukin-6 and the Interleukin-6 receptor binds to a second receptor protein, gp130, which thereupon dimerizes and initiates intracellular signaling. The gp130 receptor is present on all cells of the human body, whereas the Interleukin-6 receptor is only expressed by some cells such as hepatocytes, epithelial cells and some leukocytes. Since Interleukin-6 exhibits only measurable affinity to the Interleukin-6 receptor but not to gp130, only cells, which express the Interleukin-6 receptor can respond to Interleukin-6. It was found that the Interleukin-6 receptor can be cleaved from the cell membrane by the protease ADAM17 generating a soluble receptor. The soluble interleukin-6 receptor can still bind interleukin-6 and the complex of interleukin-6 and interleukin-6 receptor can bind to gp130 even on cells which do not express the membrane-bound interleukin-6 receptor. This mode of signaling has named Interleukin-6 trans-signaling. The protein olamkicept consists of the extracellular portion of gp130 fused (and thereby dimerized) to the constant portion of a human IgG1 antibody. Like membrane bound gp130, the protein olamkicept does not bind Interleukin-6 alone but only the complex of interleukin-6 and soluble interleukin-6 receptor. Therefore, olamkicept only inhibits interleukin-6 trans-signaling but not interleukin-6 signaling via the membrane-bound interleukin-6 receptor. It has been shown that Interleukin-6 activities via the membrane-bound interleukin-6 receptor are regenerative and protect from bacterial infections whereas interleukin-6 activities via the soluble interleukin-6 receptor are considered pro-inflammatory. Therefore, olamkicept only blocks the pro-inflammatory activities of the cytokine interleukin-6.

Research In many animal disease models of human pathologies it was tested whether the specific blockade of interleukin-6 trans-signaling by the olamkicept protein was superior to a global blockade with an interleukin-6 or an interleukin-6 receptor neutralizing antibody. It turned out that the specific blockade of Interleukin-6 trans-signaling was superior to global Interleukin-6 blockade in models of e.g. sepsis, of acute lung injury after severe acute pancreatitis and of abdominal aortic aneurysm. Furthermore, it was shown that Interleukin-6 trans-signaling plays a dominant role in colon cancer and lung cancer.

Medical use The olamkicept protein underwent phase I clinical studies in healthy volunteers and a small cohort of largely inactive patients with IBD in 2013/14. An open label phase IIa study in patients with active inflammatory bowel disesase was performed in Germany. A second placebo-controlled, phase II clinical trial in patients with ulcerative colitis was successfully completed in China, Taiwan and South Korea. The results of the German phase IIa clinical trial were published and demonstrated target engagement through olamkicept exposure over 12 weeks in patients with active inflammatory bowel disease. Most interestingly some patients developed a complete remission while others went into response. The molecular analysis revealed an olamkicept-specific signature in influencing disease pathophysiology. The results of the placebo controlled trial in China/Taiwan/South Korea were released during the 2021 Digestive Disease Week (DDW) and the 2021 annual meeting of the European Crohn's and Colitis Organization (ECCO).

References

Illustrations

Worked examples

Example 1 — a first encounter with Olamkicept

Start with the simplest possible case. Write down what Olamkicept claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Olamkicept before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Olamkicept ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Olamkicept

In research: Olamkicept appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Olamkicept in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Olamkicept is common in secondary-school and first-year university syllabi. It links to neighbouring topics Recombinant proteins, so understanding it makes those chapters shorter.
In everyday life: Look for Olamkicept outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Olamkicept in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Olamkicept means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Olamkicept out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Olamkicept in simple terms?

Why does Olamkicept matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Olamkicept?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Olamkicept.