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![NAME CLINICAL USE APPLICATION
Adalimumab
(Humira®)
Inhibition of TNF-∝
signalling
Rheumatoid arthritis
[CT]
Golimumab
(Simponi)
Inhibition of TNF-∝
signalling
Psoriatic arthritis
[CT]
AIN457 Inhibition of IL17 Psoriasis
Rheumatoid arthritis
[UR]
Examples of Fully humanised antibodies in development or undergoing clinical trials](https://image.slidesharecdn.com/immunotherapy123-250519064146-68c8f760/75/IMMUNOTHERAPY-123-pptx-855555555555555-34-2048.jpg)
IMMUNOTHERAPY 123.pptx,,,855555555555555
- 1. IMMUNOTHERAPEUTICS FORAM R ASODIYA. MPHARMACY(PHARMACOLOGY) SEM 1
- 2. CONTENT 1) IMMUNOTHERAPEUTICS 2) HUMANISATIONANTIBODY THERAPY 3) IMMUNOTHERAPEUTICS IN CLINICAL PRACTICE
- 3. 1)IMMUNOTHERAPEUTICS It isa treatment that uses certain parts of the immune system to fight disease such as cancer. It is also sometimes called biologic therapy or biotherapy. Picture credit: https://drug-dev.com/wp-content/uploads/uploads/Public/Images/0Haberman/F1.jpg
- 4. How it works? Immunotherapy includes a wide variety of treatments that work in different ways. By boosting the body’s immune system in a very general way. Helps to train the immune system to attack cancer cells specifically. Giving immune system components, such as man-made immune system proteins.
- 5. TYPES OF IMMUNOTHERAPY Themain types of immunotherapy now being used to treat cancer are: A. Monoclonal Antibodies B. Cancer Vaccines C. Non – Specific Immunotherapies D. Engineered Antibodies
- 6. A)MONOCLONAL ANTIBODIES Monoclonalantibodies are man-made proteins that act like human antibodies These Antibodies can be useful in fighting diseases because they can designed specifically to only target a certain antigen, such as one that is found on cancer cells. Many copies of a specific Antibody can be made in the lab. These are known as Monoclonal Antibodies (mAbs).
- 8. What mAbs AreMade Of? METHODS PROTEIN SOURCE TREATMENT ENDS IN 1)Murine Mouse -omab 2)Chimeric Mouse+Human -Ximab 3)Humanised Human+Mouse -Zumab 4)Human Human -umab
- 9. HOW IT WORKS? Flagging cancer cells Triggering cell-membrane destruction Blocking cell growth Preventing blood vessel growth. Directly attacking cancer cells Binding cancer and immune cells
- 10. TYPES OF MONOCLONALANTIBODIES 1. Naked mAbs are antibodies that work by themselves. 2. Conjugated mAbs . a) Radiolabeled Antibodies b) Chemolabeled Antibodies c) Immunotoxins 3. Bispecific monoclonal antibodies
- 11. 1)Naked Monoclonal Antibodies NakedmAbs can work in different ways. Some may boost a person’s immune response against cancer cells. an example is:- alemtuzumab (Campath® )- chronic lymphocytic leukemia (CLL). (binds to the CD52 antigen) Other work by blocking specific proteins that help cancer cells grow ( some may do both). For example:- trastuzumab (Herceptin)-Breast and stomach cancer (antibody against the HER2 protein)
- 12. 2)Conjugated mAbs Conjugated mAbsare also sometimes referred to as tagged, labeled or loaded Antibodies. They can be divided into groups depending on what they are linked to. a) mAbs with radioactive particles attached are referred to as radiolabeled, and treatment with this type of Antibody is known as radioimmunotherapy (RIT). b) mAbs with chemotherapy drugs attached are referred to as chemolabeled. c) mAbs attached to cell toxins are called immunotoxins.
- 13. a)Radiolabeled Antibodies For example:- Ibritumomabtiuxetan (Zevalin) mAb drug (rituximab) and a radioactive substance (Yttrium-90) an antibody against the CD20 antigen, (lymphocytes called B cells)
- 14. b)Chemolabeled Antibodies ThesemAbs have powerful chemotherapy drugs attached to them. There are only 2 chemolabeled antibodies approved by the FDA to treat cancer at this time. i. Brentuximab vedotin (Adcetris), an antibody that targets the CD30 antigen (found on lymphocytes), attached to a chemo drug called MMAE. ii. Ado-trastuzumab emtansine (Kadcyla, also called TDM-1), an antibody that targets the HER2 protein, attached to a chemo drug called DM1.
- 15. 3)Bispecific mAbs Thesedrugs are made up of parts of 2 different mAbs An example is blinatumomab (Blincyto) CD19 protein(found on some leukemia and lymphoma cells) CD3 protein(found on immune cells called T cells)
- 17. Side effects ofMonoclonal Antibodies In general, the more common side effects caused by Monoclonal Antibody drugs include : Allergic reaction, such as hives or itching. Flu – like symptoms, including chills, fatigue, fever, muscle aches and pains. Nausea Diarrhea Skin rashes
- 18. B)CANCER VACCINES Cancer vaccinesare made from Dead cancer cells, proteins from cancer cells, or immune system cells.
- 19. HOW IT WORKS? Theseuse your immune system to a) prevent cancer b) treat cancer
- 20. a) Prevent cancer b)Treat cancer VACCINES TREATMENT OF Sipuleucel-T Prostate Cancer Talimogene laherparvec(T-VEC) Melanoma skin cancer BCG Early stage Bladder cancer VACCINES ACTS AGAINST PREVENTION OF Cervarix Hpv (Human papilloma virus) Cervix,Throat,Vagina, Vulva,Anus and penis cancer Gardasil Gardasil-9 Heplisav-B Hbv infection Liver Cancer
- 21. Side effects ofcancer vaccines Side effects are usually mild and can include. Fever Chills Fatigue Back and joint pain Nausea Headache A few men may have more severe symptoms, including problems breathing and high blood pressure.
- 22. C)Non- Specific Immunotherapies Non- specific immunotherapies don’t target cancer cells specifically. Cytokines Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. a. Interleukins b. Interferons
- 23. a)Interleukins Interleukins are agroup of cytokines that act as chemical signals between white blood cells. Interleukin-2 (IL-2) man-made version of IL-2 (advanced kidney cancer and metastatic melanoma) IL-7, IL-12, and IL-21*
- 24. b)Interferons Interferons are chemicalsthat help the body resist virus infections and cancers. IFN-alfa IFN-beta IFN-gamma
- 25. IFN-alfa • Hairy cellleukemia • Chronic myelogenous leukemia (CML) • Follicular non-Hodgkin lymphoma • Cutaneous (skin) T-cell lymphoma • Kidney cancer • Melanoma • Kaposi sarcoma
- 26.
- 27. 2)HUMANISATION ANTIBODY THERAPY Humanized antibodies are antibodies from non- human species Whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.
- 28. Shortfalls in murineantibodies A short half-life in vivo (due to host immune rejection); – limited penetration into target cells (such as tumour site), and – Being 100% murine proteins, and are recognised as ‘foreign’ by the human body and therefore they are rejected by an antibody- mediated immune response (human anti-murine antibodies –HAMA; produced by the host) To overcome these problems novel chimeric and humanised antibodies have been developed
- 29. Production of humanisedAntibodies Humanised Antibodies are produced by grafting murine hypervariable amino acid domains into human antibodies. This results in a molecule of approximately 95% human origin.
- 30. Uses of humanisedAntibodies It includes: Reduction in the immunogenicity of an antibody Therapeutic value of an antibody increases after humanization.
- 31.
- 32. NAME CLINICAL USECLINICAL APPLICATION Infliximab (Remicade®) Anti-inflammatory (against TNF ) ∝ Rheumatoid arthritis, Crohns disease, Ulcerative colitis Basiliximab (Simulect®) Anti-inflammatory (against IL-2 receptor) Against graft rejection in kidney transplants Rituximab (Rituxan® and MabThera®) Anti-cancer (against the protein CD20) Non-Hodgkins lymphoma Cetuximab (Erbitux®) Anti-cancer (EGFR Inhibitor) Colorectal cancer, Head and Neck cancer Abciximab (ReoPro®) Anti-coagulant (glycoprotein IIb/IIIa receptor antagonist) Prevent coagulation during coronary angioplasty, IHD and unstable angina Examples of Chimeric antibodies that are used in clinical practice EGFR=Epidermal growth factor receptor
- 33. NAME CLINICAL USECLINICAL APPLICATION Bevacizumab (Avastin®) Angiogenesis Inhibitor (against VEGF) Colorectal cancer, Certolizumab pegol (Cimzia®) TNF- Signaling inhibitor ∝ Crohns disease Rheumatoid arthritis Daclizumab (Zenapax®) Against IL-2R receptor ∝ Currently in clinical trials to suppress graft rejection Palivizumab (Synagis®) Against F protein of respiratory syncytial virus Respiratory syncytial viral infections Examples of Humanised antibodies that are used in clinical practice VEGF=vascular endothelial growth factor
- 34. NAME CLINICAL USEAPPLICATION Adalimumab (Humira®) Inhibition of TNF-∝ signalling Rheumatoid arthritis [CT] Golimumab (Simponi) Inhibition of TNF-∝ signalling Psoriatic arthritis [CT] AIN457 Inhibition of IL17 Psoriasis Rheumatoid arthritis [UR] Examples of Fully humanised antibodies in development or undergoing clinical trials
- 35. REFERNCES Picture credit: https://drug-dev.com/wp-content/uploads/uploads/Public/Images/0Haberman/F1.j pg https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/ immunotherapy/monoclonal-antibodies.html https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal- antibody/art-20047808 https://www.researchgate.net/profile/Patrizia-Mondello/publication/286983293/ figure/fig1/AS:317092550201344@1452612163909/The-radio-labeled-antibody-90-Y- ibritumomab-tiuxetan-Zevalin-binds-to-cells-with-CD20.png Pic credit https://www.researchgate.net/figure/Mechanism-of-blinatumomab-therapeutic-act ion-recruitment-of-T-cells-to-tumors-through_fig3_322637149 https://www.webmd.com/cancer/immunotherapy-treatment-types https://oralcancerfoundation.org/treatment/cancer-immunotherapy/non-specific- cancer-immunotherapies-adjuvants/
- 36.