Immunotherapeutics

This slideshare conatins detailed overview of immunotheraphy,humanisation of antibodies and its clinical application
this is the topic from cellular and molecular pharmacology of m pharmacy first year
immunotheraphy is further classified to its various types which has been discussed individually
its also conatins various immunotheraphy drugs which has other clinical advantages

1.   IMMUNOTHERAPEUTICS Jayhind l Bharti M pharmacy(pharmacology) Sem 1

2. CONTENT 1) IMMUNOTHERAPEUTICS  2) HUMANISATION ANTIBODY THERAPY 3) IMMUNOTHERAPEUTICS IN CLINICAL PRACTICE

3. 1)IMMUNOTHERAPEUTICS  

4. 1)IMMUNOTHERAPEUTICS   It is a 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

5. 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.

6. TYPES OF IMMUNOTHERAPY The main types of immunotherapy now being used to treat cancer are: Monoclonal Antibodies Cancer Vaccines Non – Specific Immunotherapies Engineered Antibodies

7. A)MONOCLONAL ANTIBODIES Monoclonal antibodies 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 mA bs Are Made 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 MONOCLONAL ANTIBODIES 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 Naked mAbs 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 mAbs are also sometimes referred to as tagged, labeled or loaded Antibodies. They can be divided into groups depending on what they are linked to. mAbs with radioactive particles attached are referred to as radiolabeled , and treatment with this type of Antibody is known as radioimmunotherapy (RIT). mAbs with chemotherapy drugs attached are referred to as chemolabeled . mAbs attached to cell toxins are called immunotoxins.

13. a) Radio labeled Antibodies For example:- Ibritumomab tiuxetan ( Zevalin ) mAb drug (rituximab) and a radioactive substance (Yttrium-90) an antibody against the CD20 antigen, (lymphocytes called  B cells )

14. b ) Chemolabeled Antibodies  These mAbs have powerful chemotherapy drugs attached to them. There are only 2 chemolabeled antibodies approved by the FDA to treat cancer at this time. Brentuximab vedotin ( Adcetris ), an antibody that targets the CD30 antigen (found on lymphocytes), attached to a chemo drug called  MMAE . Ado-trastuzumab emtansine ( Kadcyla , also called TDM-1), an antibody that targets the HER2 protein, attached to a chemo drug called DM1 .

15. 3 ) B ispecific mAbs These drugs 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 )

16. Side effects of Monoclonal 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

17. B)CANCER VACCINES Cancer vaccines are made from D ead cancer cells, proteins from cancer cells, or immune system cells.

18. HOW IT WORKS? These use your immune system to prevent cancer treat cancer

19. 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 Hpv Gardasil-9 Hpv Heplisav -B Hbv infection Liver Cancer

20. Side effects of cancer 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.

21. 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. Interleukins Interferons

22. a) Interleukins Interleukins are a group 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*

23. b ) Interferons Interferons are chemicals that help the body resist virus infections and cancers. IFN-alfa IFN-beta IFN-gamma

24. IFN-alfa Hairy cell leukemia Chronic myelogenous leukemia (CML) Follicular non-Hodgkin lymphoma Cutaneous (skin) T-cell lymphoma Kidney cancer Melanoma Kaposi sarcoma

25. 2)HUMANISATION ANTIBODY THERAPY

26. 2)HUMANISATION ANTIBODY THERAPY Humanized antibodies are antibodies from non- human species W hose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.

27. Shortfalls in murine antibodies A short half-life in vivo (due to host immune rejection); – limited penetration into target cells (such as tumour site), and – B eing 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

28. Production of humanised Antibodies  Humanised Antibodies are produced by grafting murine hypervariable amino acid domains into human antibodies. This results in a molecule of approximately 95% human origin.

29. Uses of humanised Antibodies  It includes: Reduction in the immunogenicity of an antibody Therapeutic value of an antibody increases after humanization.

30. 3 ) IMMUNOTHERAPEUTICS IN CLINICAL PRACTICE

31. NAME CLINICAL USE CLINICAL 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

32. NAME CLINICAL USE CLINICAL 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

33. 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

34. REFERNCES Picture credit: https://drug-dev.com/wp-content/uploads/uploads/Public/Images/0Haberman/F1.jpg 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-action-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/

35. THANK YOU!