PPT on monoclonal antibodies, Pharmacology, B Pharm 6th sem

1. MONOCLONAL ANTIBODIES (MAB)

2. Immunoglobulins (Ig)
• Naturally occurring antibodies, present in Serum and cells of immune system.
• Structurally glyco-proteins.
• Lower part of Ig – Carbohydrates ; Upper part of Ig – Proteins (amino acids)
• 2 different chains – Heavy and light chains (2 each)
• Light chain – Low mol. Weight due to less no. of Amino acids (around 330)
• Heavy chain – High mol. weight due to more no. of Amino acids (almost 3 times
= 990)
• B/w and within Heavy and Light chains – Disulphide bonds.

3. STRUCTUAL FEATURES
 Two regions - Fab and Fc
1) Fab
• Stands for Fragment Antigen Binding.
• More choice of interest.
• Consists of Variable region and Constant region.
a) Variable region – Capable of changing amino acids sequence.
Antigen binds here (Epitope sequence).
Hyper variable region (almost 110 amino acids)
b) Constant region - Does not show variations in amino acids sequence.
2) Fc
• Stands for Fragment Crystallizable region.
• Present at Tail region of antibody.
• Interacts with cell surface receptors (Fc receptors) and some proteins of
the compliment system.

4. Ig
G A M D E
γ Type α Type μ Type δ Type ε Type

5. MAB
MAB
Recognize
specific
antigen
Ultra-
sensitive
Hybrid
Immune
system
derived
proteins

6. • Purified antibodies.
• Produced by single cell / clone of cell [In-Vitro]
• Engineered to recognize and bind to a specific and single antigen to provide Passive immunity.
• To produce MAB, animal is immunized with antigen that will yield desired antibody.
• Antibody producing cells are removed and mixed with Myeloma cells under condition that promote cell fusion.
• Resulting hybrid cell grow indefinitely and produce MAB.
• APPLICATIONS –
1) For Diagnostic purpose (ELISA).
2) Targeted attack on Cancer cell (mop up cancer cells after chemotherapy).
3) Detect allergies, anaemias, heart disease.
4) Diagnostic kits are available for performing Drug assay, blood typing, Hepatitis, Gonorrhoea, AIDS, etc.
5) For developing immunotoxins.
INTRODUCTION

7. PRODUCTION OF MAB
• Technique was given by Kohler and Milstein (1975).

8. NOMENCLATURE AND CLASSIFICATION
• Usually name ends with mab (Ex – Rituximab).
• But some monoclonal antibodies are not stable, so fusion proteins are attached in order to
stabilize it.
• If it contains fusion protein, then the name will end with cept (Ex – Rilonacept).
• Before mab, the letters tell about Source of antibody.

9. SOURCE LETTERS BEFORE mab EXAMPLE PROPERTIES (SOURCE BASED)
Animal mo (mice) Muromonomab • High risk of allergy and antigenicity.
• Not commonly used.
Purely Human u Panitumumab • Least risk of allergy and antigenicity.
Mixed Chimeric xi Infliximab • 50-50 % mixture each.
Mixed Humanized zu Trastuzumab • Mostly human with a small amt. of
animal component.

10. • Before source, the letters tell about Target of monoclonal antibodies.
TARGET LETTERS BEFORE SOURCE EXAMPLE USE
Tumour tu
Cetuximab
Rituximab
Trastuzumab
Pertuzumab
Anti-cancer
Virus vi Palivizumab Against Respiratory
syncytial virus
Circulation ci Abciximab
Bevacizumab
Anti-platelet
Inhibits angiogenesis
Osteo (Bone) os Denosumab In osteoporosis
Hyper Cholesterol oc Alirocumab
Evolocumab
Over cholesterol
To lower the
immunity
li
Adalimumab
Certolizumab
Etanercept*
Infliximab
Golimumab
Daclizumab
Basiliximab
Rheumatoid Arthritis
Crohn’s disease
Transplantation
TNF α
inhibitors
IL-2
inhibitors

11. TARGET LETTERS BEFORE SOURCE EXAMPLE USE
To lower the
immunity
li
Efalizumab
Natalizumab
Eculizumab
Omalizumab
Psoriasis
Multiple sclerosis
Paroxysmal Nocturnal
Hemoglobinuria
Bronchial Asthma