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) HUMANISATIONANTIBODYTHERAPY
3) IMMUNOTHERAPEUTICS INCLINICAL 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
system proteins.

6. TYPES OF IMMUNOTHERAPY
The main types of immunotherapy now being used to treat cancer are:
A. MonoclonalAntibodies
B. CancerVaccines
C. Non – Specific Immunotherapies
D. EngineeredAntibodies

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
found on cancer cells.
 Many copies of a specificAntibody can be made in the lab.These are known as
are known as MonoclonalAntibodies (mAbs).

9. What mAbs 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

10. 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

11. TYPES OF MONOCLONAL ANTIBODIES
1. Naked mAbs are antibodies that work by themselves.
2. Conjugated mAbs .
a) RadiolabeledAntibodies
b) Chemolabeled Antibodies
c) Immunotoxins
3. Bispecific monoclonal antibodies

12. 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)

13. 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.
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.

14. a)Radiolabeled 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)

15. 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.
i. Brentuximab vedotin (Adcetris), an antibody that targets the CD30 antigen
CD30 antigen (found on lymphocytes), attached to a chemo drug
called MMAE.
ii. Ado-trastuzumab emtansine (Kadcyla, also calledTDM-1), an antibody that
antibody that targets the HER2 protein, attached to a chemo drug called
DM1.

16. 3)Bispecific 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)

18. Side effects of Monoclonal Antibodies
In general, the more common side effects caused by MonoclonalAntibody drugs
include :
 Allergic reaction, such as hives or itching.
 Flu – like symptoms, including chills, fatigue, fever, muscle aches and pains.
 Nausea
 Diarrhea
 Skin rashes

19. B)CANCER VACCINES
Cancer vaccines are made from
 Dead cancer cells,
 proteins from cancer cells,
 or immune system cells.

20. HOW IT WORKS?
These use your immune system to
a) prevent cancer
b) treat cancer

21. 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,Vul
va,Anus and penis
cancer
Gardasil
Gardasil-9
Heplisav-B Hbv infection Liver Cancer

22. 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.

23. 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

24. 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*

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

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

27. 2)HUMANISATION ANTIBODY
THERAPY

28. 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.

29. 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 –
 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

30. 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.

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

32. 3) IMMUNOTHERAPEUTICS
IN CLINICAL PRACTICE

33. 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

34. 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

35. 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

36. 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/

37. THANK YOU!