- Monoclonal antibodies are monospecific antibodies produced by identical immune cells that are clones of a single parent cell. They bind to the same epitope. - George Kohler and Cesar Milstein first developed the hybridoma technique in 1975 to produce monoclonal antibodies in large quantities. - There are four main types of monoclonal antibodies: murine, chimeric, humanized, and human. Therapeutic monoclonal antibodies are used to treat conditions like cancer, autoimmune diseases, infections, and asthma. They have revolutionized medicine and many new applications are still being developed.

1. - Aarati K.C
- Chhabi Acharya
B.Pharmacy
HOPE Int’l College
Monoclonal Antibodies'
Popular Drugs

2. We will discuss about:
• Introduction
• History
• Types (with example)
• Pharmacokinetic profile
• Therapeutic uses (with specific drug)
• Future Aspect
• Conclusion

3. Introduction:
• Monoclonal antibodies (mAb or moAb)
are monospecific antibodies that are the same
because they are made by identical immune cells
that are all clones of a unique parent cell.
• Monoclonal antibodies have monovalent affinity, in
that they bind to the same epitope.
• Monoclonal antibodies that specifically bind to
substance; they can then serve to detect or purify
that substance.
• This has become an important tool
in biochemistry, molecular biology and medicine.

4. History:
• 1975: Hybridoma
Technology
George Kohler and Cesar
Milstein devised a method
to obtain large amounts of a
mAb
• 1984: Noble prize for
medicine
• 1988: Greg winter et. al
pioneered the techniques to
humanize monoclonal
antibodies
Cesar Milstein & George Kohler

5. Types of mAb:
• Murine
• Chimeric mAb
• Humanized mAb
• Human mAb

6. 1.Murine:
• Derived from mice murinae.
• Patients treated with murine mAbs develops human
antimouse antibodies(HAMA)
• Rapid clearance of the mAbs.
• Poor tumor penetration.
• Hypersentivity reaction.

7. 2.Chimeric mAbs:
• Antigen binding parts(variable region) of mouse Ab
with effector parts (constant region)of human
• E.g.:
- Infliximab
- Abciximab
- Rituximab

8. 3.Humanized mAb:
• Human antibody with complimentary determining
region(CDR) or hyper variable region from non
human sources
• E.g.:
- Daclizumab
- Trastuzumab

9. 4. Human mAb:
• Human monoclonal antibodies are
produced using transgenic mice.
• Human monoclonal antibodies are
produced by transferring human
immunoglobulin genes into the murine
genome, after which the transgenic mouse
is vaccinated against the desired antigen,
leading to the production of monoclonal
antibodies, allowing the transformation of
murine antibodies in vitro into fully human
antibodies.

10. Pharmacokinetics:
• Routes of administration:
- Subcutaneously: Rituximab, trastuzumab, adalimumab
- Intramuscularly: Palirizumad
• Half-life:
- Chimeric: 4-15 days
- Humanized: 3-24 days
- Recombinant human:11-24days
- Human antimouse antibody (HAMA) response
develops 7-10 days following exposure to murine
antibody.

11. Therapeutic Uses:
1. Immuno Suppression
- Autoimmune diseases
2. Malignancies
3. Antiplatelet therapy
4. Asthma
5. Osteoporosis

12. 1.Immuno suppression:
• Muromonab: CD-3-murine mAbs
• 1st
mAb approved for clinical use in humans.
• Act on CD3 receptors.
• Apoptosis of the T-cell.
• Prevents graft rejection in renal transplant.
• ADRs: Skin reaction, fever, chills, headaches,
nausea, and diarrhea etc.

13. Autoimmune disease
• Epratuzumab:
- Humanized antibodies that binds to the glycoprotein
CD22 of mature and malignant B-cells.
• Efalizumab:
- Humanized antibody that binds with CD11 a subunit of
lymphocytes function associated antigen 1.
- Therapeutic uses: Plague psoriasis.
- ADR: Bacterial sepsis, viral meningitis, invasive fungal
disease

14. 2.Magligencies:
• Rituximab: First chimeric IgG-I mAb Mechanism of
action: Directed against CD 20 on B cells.
• Cetuximab: Chimeric Ab Directed against EGFR
Inhibits tumor growth
- Therapeutic use: Metastatic colorectal cancer, head
and neck cancer.
• Bevacizumab: Humanized mAb
- MoA: Directed against VEGF Blocks VEGF in
neovascularisation.

15. - Therapeutic uses: Metastatic colorectal ca, Pancreatic
ca, Breast cancer Prostate cancer.
• Trastuzumab: Humanized Ab.
- Therapeutic uses: Metastatic breast cancer.

16. 3.Antiplatelet therapy:
• Abciximab: Chimeric mAb
• MOA: - Glycoprotein iib/iiia receptor antagonist.
- Prevent platelet aggregation
- Inhibits fibrinogen
• Therapeutic uses:
- Acute coronary syndrome
- PCI
• ADR:
- Increase risk of bleeding, thrombocytopenia.

17. 4.Asthma
• Omalizumab: Humanized Ab
• MOA: - Binds IgE
- Interaction with
basophils and mast cells.
• Therapeutic uses: Asthma in
adults and adolescents
refractory to inhaled
corticosteroid therapy.

18. 5.Osteoporosis:
• Denosumab: Human mAb
• Act against rank ligand
• Approved by FAD for use in
postmenopausal women with
risk of osteoporosis.
• ADR: Urinary tract infection,
constipation, rashes and joints
pain.

19. Future aspect:
• Lpilimumab: Human monoclonal antibodies.
• Undergoing clinical trials treatment of melanoma
• Zanolimumab: CD4 specific mAb
• Cutaneous T-cell lymphoma
• Phase iii clinical trial
• Others uses: Diagnostics:
• HIV diagnostics kit
• A mAb can be used to detect pregnancy only 14
days after conception.
• Other mAb allow rapid diagnosis of hepatitis.

20. Conclusion:
• MAbs are highly specific Abs produced by a clone
of single hybrid cells formed by fusion of B cell
with the tumor cell.
• The hybridoma formed yields higher amount of
MAbs. MAbs can be produced in vitro and in vivo .
• Recombinant DNA technology, genetic
engineering and transgenic animals are used to
produce humanized MAbs or pure human MAbs,
with fewer ADRs Used for treatment of cancer,
autoimmune disorders, graft rejections, infections,
asthma etc.

21. References:
• Dr. Haramjit Singh, Monoclonal antibodies and
their role in pharmacology, 19th
July 2012
• http://www.imgt.org/IMGTrepertoire/GenesClinical/mon
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC287422/