- Aarati K.C
- Chhabi Acharya
HOPE Int’l College
We will discuss about:
• Types (with example)
• Pharmacokinetic profile
• Therapeutic uses (with specific drug)
• Future Aspect
• 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
• This has become an important tool
in biochemistry, molecular biology and medicine.
• 1975: Hybridoma
George Kohler and Cesar
Milstein devised a method
to obtain large amounts of a
• 1984: Noble prize for
• 1988: Greg winter et. al
pioneered the techniques to
Cesar Milstein & George Kohler
Types of mAb:
• Chimeric mAb
• Humanized mAb
• Human mAb
• Derived from mice murinae.
• Patients treated with murine mAbs develops human
• Rapid clearance of the mAbs.
• Poor tumor penetration.
• Hypersentivity reaction.
• Antigen binding parts(variable region) of mouse Ab
with effector parts (constant region)of human
• Human antibody with complimentary determining
region(CDR) or hyper variable region from non
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
• Routes of administration:
- Subcutaneously: Rituximab, trastuzumab, adalimumab
- Intramuscularly: Palirizumad
- 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
• Muromonab: CD-3-murine mAbs
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.
- Humanized antibodies that binds to the glycoprotein
CD22 of mature and malignant B-cells.
- 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
• 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
- Therapeutic uses: Metastatic colorectal ca, Pancreatic
ca, Breast cancer Prostate cancer.
• Trastuzumab: Humanized Ab.
- Therapeutic uses: Metastatic breast cancer.
• Omalizumab: Humanized Ab
• MOA: - Binds IgE
- Interaction with
basophils and mast cells.
• Therapeutic uses: Asthma in
adults and adolescents
refractory to inhaled
• 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
• 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.
• 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,
• Dr. Haramjit Singh, Monoclonal antibodies and
their role in pharmacology, 19th