Monoclonal antibodies

1. MONOCLONAL ANTIBODIES
By
Dr. Elza Joy Munjely
JR III
Dpmt of Pharmacology
Govt.Medical College,Kottayam

2. Those antibodies which are
produced by a single clone of B
lymphocytes and are directed
against a single antigenic
determinant

3. How are they made?
Hybridoma technology
Hybridoma = Specific B-lymphocyte
+
Mouse myeloma cell
• Retains the antibody forming ability of B-lymphocyte &
the ability of myeloma cell to proliferate endlessly

4. Hybridoma Technology
1975, Georges Köhler and Cesar Milstein
- Nobel Prize in1984

5. Mouse immunized with antigen X
Spleen cells
Cell-culture
Myeloma line
Myeloma cells
Fused in Polyethylene
Glycol to produce
Hybridomas
Transfered to
HAT mediumUnfused
plasma &
myeloma
Cells die
Hybridomas that
produce antibodies
specifically against
Antigen X are
selected & Grown
in bulk
Monoclonal
antibodies

6. Light chain
Heavy
chain
Variable regions
Of heavy &
Light chains
Constant regions
Of heavy &
Light chains
ANTIBODY

7. Classification
Murine Chimeric Humanised Human
Highly
immunogenic
Least
immunogenic
100% mouse 30% mouse 5-10% mouse 100% human

8. Nomenclature
• tu - tumour
• vi - virus
• ci - circulation
• If no prefix - immunomodulator
Murine Chimeric Humanised Human
omab ximab zumab umab

9. Examples
Murine Chimeric Humanised Human
omab ximab zumab umab
•Muromonab •Rituximab
•Abciximab
•Infliximab
•Alemtuzumab
•Bevacizumab
•Trastuzumab
•Omalizumab
•Palivizumab
•Adalimumab

10. Armed & unarmed monoclonal Abs
‘Unarmed / Naked’ Armed
Not fused to a toxin Fused with a toxin or a radioisotope
Acritumomab - labeled with Technetium 99
immunoscintigraphy
Ibritumomab - labeled with Yttrium 90
relapsed/refractory
low grade follicular/B-cell
NHL

11. Mechanisms of anti-tumour effects of
MAbs
• ADCC-Antibody dependent cellular
cytotoxicity
• CDC-Complement dependent cytotoxicity
• Immunomodulation
• Altering signal transduction

12. Pharmacokinetics
• Routes of administration:
– Subcutaneously (Rituximab, Trastuzumab, Adalimumab)
– Intramuscularly (Palivizumab)
– Intravenously
• IV route: preferred because of 100% bioavailability
• Route for elimination of antibodies
– Via uptake & catabolism by reticuloendothelial system &
target tissue.

13. • Patients treated with murine mAbs develop a Human
Antimouse Antibody (HAMA) response which develops 7–
10 days following exposure to murine antibody
– Rapid clearance of the mAb
– Poor tumour penetration
– Hypersensitivity reactions
• Half-life
– Chimeric : 4 –15 days
– Humanized: 3 - 24 days
– Recombinant human: 11– 24 days
Pharmacokinetics

14. • Allergic reactions, such as hives or itching
• Flu-like symptoms, including chills, fatigue, fever, muscle aches
and pains
• Nausea
• Diarrhea
• Skin rashes
• Infection - infliximab
• Bone marrow suppression
• Cardiomyopathy – Trastuzumab
• Thromboembolism - Bevacizumab
Side effects of monoclonal antibody

15. Uses of Mabs
THERAPEUTIC USES
Malgnancies
Auto immune disease
Asthma
DIAGNOSTIC APPLICATONS
In western blot, ELISA, RIA,
flow cytometry, Immunodot blot,
pregnancy detection etc.

16. THERAPEUTIC CLASSIFICATION
1. Antitumor MABs
2. MABs Used to Deliver Isotopes & Toxins to
Tumors
3. MABs Used as Immunosuppressants & Anti-
Inflammatory Agents
4. Other MABs

17. Antitumor
MABs
MABs Used to
Deliver Isotopes &
Toxins to Tumors
MABs Used as
Immunosuppressa
nts & Anti-
Inflammatory
Agents
1. Alemtuzumab
2. Bevacizumab
3. Cetuximab
4. Panitumumab
5. Rituximab
6. Trastuzumab
Toxin-linked MAbs :
• Gemtuzumab
ozogamicin
Radioisotope
carrying MAbs :
•Ibritumomab (90Y)
•Tositumomab (131I)
1. Muromonab-Anti
CD-3 antibody
2. Daclizumab,
Basiliximab-IL-2
receptor
antagonists
3. Infliximab,
Adalimumab-
TNFα inhibitors:
4. Omalizumab-
Anti-IgE antibody

18. List of some important Mab
Therapeutic agent Indication
• Alemtuzumab (CD52) B cell CLL
• Bevacizumab (VEGF) Met. Colorectal cancer
• Ranibizumab (VEGF-A) Neovas. Macular degeneration
• Cetuximab (EGFR) Met. Colorectal cancer
• Gemtuzumab (CD33) AML
• Panitumumab (EGFR) Met. Colorectal cancer
• Rituximab (CD20) Low grade NHL
• Trastuzumab (HER-2/neu) Met. Breast cancer
• Eculizumab (C5) PNH

19. List of some important Mab
Therapeutic agent Indication
• Basiliximab (IL-2 Receptor) Renal, heart transplant
• Daclizumab (IL-2 Receptor) Renal transplant, M.Sclerosis
• Efalizumab (CD11a) Psoriasis
• Adalimumab (TNF α) RA
• Infliximab (TNF α) RA
• Abciximab (GPIIb/IIIa receptor Acute coronary syndrome
on activated platelets)
• Omalizumab (IgE Ab) Allergic asthma
• Palivizumab RSV infection
• Natalizumab (integrins) M.Sclerosis,Crohn’s disease

20. Thankyou