Interleukin

1. Interleukin 组员：缪李信李群陈鹏军 梁烁 杨瑞瑞杨丽李亚琳 张丽

2. What’s interleukin? A biological response modifier (substance that can improve the body's natural response to infection and disease) that helps the immune system fight infection and cancer. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases.

3. Interleukin plays an important role in immune response

4. IL-1 function Functions of IL-4 and IL-6

5. Due to its effects on T-cells and B-cells IL2 is a central regulator of immune responses.

6. INTERLEUKIN-2 SOURCES PROTEIN CHARACTERISTICS RECEPTORS BIOLOGICALACTIVITIES CLINICAL USE Company Logo

7. sources • Under physiological conditions IL2 is produced mainly by T-cells expressing the surface antigen CD4 following cell activation by mitogens or antigens. • Resting cells do not produce IL2 • Transformed T-cells and B-cells, leukemia cells, LAK cells (lymphokine-activated killer cells) and NK-cells also secrete IL2. • Vitamin E can enhance the production of IL2

8. PROTEIN CHARACTERISTICS IL2 is a protein of 133 amino acids (15.4 kDa) with a slightly basic pI. It does not display sequence homology to any other factors. L2 is synthesized as a precursor protein of 153 amino acids with the first 20 aminoterminal amino acids functioning as a hydrophobic secretory signal sequence. The protein contains a single disulfide bond (positions Cys58/105) essential for biological activity.

9. The molecular constitution of IL-2

10. Receptor of IL-2 • The biological activities of IL2 are mediated by a membrane receptor that is expressed almost exclusively on activated, but not on resting, T-cells . Activated B-cells and resting mononuclear leukocytes rarely express this receptor. The expression of the IL2 receptor is modulated by IL5 and IL6. For other factors specifically influencing IL2 receptor expression see: IL2R/p55 inducing factor, IL2 receptor inducing factor, IL2R-alpha chain inhibitory activity. Company Logo

11. Three different types of IL2 receptors low affinity receptor high affinity IL2 receptor intermediate affinity IL2 receptor This receptor is a membrane receptor complex consisting of the two subunits:p75 and p55as the ligand binding domains and a gamma chain as a signaling component (Kdis = 100 pM) consists of the p75 subunit and a gamma chain. (Kdis = 10 nM) is formed by p55 alone. Company Logo

12. Molecular structure of IL-2 receptor

13. A B C IL-2 promote the proliferation of CD4+ and CD8+ T cell Promote the expression of various receptors on T cell Such as:TfR(转铁蛋白受体), Insulin receptor Promote the T cell to produce lymphokines. Such as: IFN-γ,IL-4,IL-5,IL-6,CSF 1.IL2 functions on CD4+ and CD8+ T cells Company Logo

14. IL-2 promote the proliferation of CD4+ T cell

15. 2.Promote the differentiation and effect of killer cell

16. 3.Effect on B cell directly and indirectly. Indirect: IL-2 IL-2R on T cell secret Some factors to B cell Direct: IL-2 B cell Plasma cell Ab + Ig

18. 4.Activate macrophage IL-2 promotes the microphage to kill the tumor according the mechanism of ADCC.

19. Clinical application and significance IL2 displays significant anti-tumor activity for a variety of tumor cell types since it supports the proliferation and clonal expansion of T-cells that specifically attack certain tumor types .

20. Adoptive immunotherapy Definition: • Based on the idea that the immune system can delay tumor growth. • It involves several steps : 1: Remove lymphocytes from the patient. 2: Stimulate those lymphocytes in vitro by the IL-2 and other activators to increase their immune capabilities. 3: Transfer those cells back into the patient to fight against the cancer. ------ There are many kinds of effect cells.

21. LAK cell LAK cells are developed by removing peripheral blood lymphocytes and stimulating them with high concentrations of interleukin 2 (IL-2) (a cytokine produced by lymphocytes that stimulates both T-cells and natural killer cells). Once there is a large enough quantity of stimulated cells, the cells are transferred back into the patient. The adoptive transfer of these cells has shown promise in preclinical models. www.soppt.cn

22. TIL Cell • Tumor tissue contains its own immune system cells called tumor infiltrating lymphocytes. In TIL therapy, tumor infiltrating lymphocytes are removed from the tumor itself and treated with IL-2. These activated cells are then returned to the patient to attack the tumor.

23. CTL cell

24. Other therapy • Cytokine therapy IL-2,TNF-,IFN-,CSF • Gene therapy Cytokine gene tumor antigen gene anti-oncogene MHC gene

25. Case 1 According to the National Cancer Institute,interleukin-2 (IL-2) is a type of biological response modifier (a substance that can improve the body's natural response to infection and disease) that stimulates the growth of certain disease-fighting blood cells in the immune system. These substances are normally produced by the body. When the treatment is effective, it works very well. As you can see in the first graphic, the computed tomography (CT) photo shows a kidney tumor highlighted on the left in a red circle. After completing IL-2 therapy, the tumor appears to be gone (green circle).

26. Case 2 Here is another example of IL-2 therapy at work. It’s a treatment of a patient with melanoma(黑素瘤). The after photo on the right shows that multiple tumors are gone with little scarring.

27. Other clinical application Cellular immunodeficiency diseases, especially those with impaired IL2 production are successfully treated by daily injections of hIL2. IL2 is also effective on some patients with antibody deficiency, probably caused by the lack of T-cell help for B-cells. A number of diseases have been described to be associated with the aberrant expression of IL2 or IL2 receptors, including Hodgkin's disease, Graft-versus-Host reaction, AIDS, immunodeficiency syndrome, severe burn traumas (see also: inflammation, wound healing), and allogenic bone marrow transplantation.

28. Pay Attention to Proper Dose ! On the contrary high dose IL2 therapy, accordingly, is also associated with a great number of unwanted toxic side-effects. IL2 has additional effects on other components of the cellular immune system, including B-cells and macrophages, and induces the secretion of other soluble mediators, including TNF-alpha, TNF-beta, and IFN-gamma. These effects may contribute to the antitumor activity of IL2 as well as to its dose-related toxicity. Several studies have demonstrated that the application of intratumoral low doses of IL2 can be highly effective against cancer and without toxic side-effects.

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