monoclonal antibodies drug targeting particulate carrier system presented by : - Roshan Lal Singh student of M.pharma 2nd semester University institute of pharmacy Pt. R. S. U. Raipur (C.G.).

1. Monoclonal antibody Drug
Targeting Particulate Carrier System
Presented by
Roshan Lal Singh
M.Pharma 2nd sem.
University institute of pharmacy
Pt. R. S. U. Raipur

2. Contents
1.Introduction
2.Role of antibody in immune system
3.Need to develop monoclonal antibodies
4. type of monoclonal antibodies
5.Monoclonal antibodies –based targeted drug
delivery
6.Advantages and disadvantages
7.Application

3. INTRODUCTION
Antibodies are produced by a specialized group of cells called B-
Lymphocytes.
Monoclonal antibodies (mAb) are antibodies that are identical
because they were produced by one type of immune cell, all clones
of a single parent cell. mAb are the antibodies that are identical
because they were produced by one type of immune cell (B cell), all
clones of a single parent cell.

4. An antibody is a protein used by the immune system to identify and neutralize
foreign objects like bacteria and viruses. Each antibody recognizes a specific
antigen unique to its target.
Polyclonal antibodies are antibodies that are derived from different cell
lines. They differ in amino acid sequence.

5. Role of Antibody in Immune System
• Each Antigen has specific antigen determinants (epitopes) located on it.
The antibodies have complementary determining regions (CDRs). These are
mainly responsible for the antibody specificity.
• Each antigen has several different epitopes on it. They are recognized by
many different antibodies. All these antibodies thus produced act on the
same antigen. Hence these are designated as polyclonal antibodies.

6. Need to develop monoclonal antibodies
• In general naturally produced antibodies are non-specific and
heterogeneous in nature. Hence there are several limitations in the use of
polyclonal antibodies for therapeutic and diagnostic purposes.
• Thus there is a need for producing monoclonal antibodies for different
antigens.

7. The structure of antibodies

8. Types of monoclonal antibodies

9. Murine monoclonal antibodies
Murine monoclonal antibodies that is
synthesis by hybridoma technology and
direct against the glycoprotein CD3
antigen of human T cell.
it used i.v. for treatment acute rejection
of renal cardiac, and hepatic transplant
patients. Example: - cetuximab,
ibritumomab

10. Chimeric mAb
chimers combine the human
constant regions with the intact
rodent variable regions.
Affinity and specificity
unchanged. Also cause human
antichimeric antibody response
(30% murine resource)
Example: - rituximab

11. Humanized mAb
Humanized mAbs::
contained only the
CDRs of the rodent
variable region grafted
onto human Framework
Regions [FR] Example: -
trastuzumab

12. Monoclonal antibody – based targeted drug delivery
Immunoglobulin develop against a surface determinants after
immobilization on particulate or colloidal delivery system could
targeted a cell bearing Fc receptor via their Fc region or to the target
antigen on the cell surface through Fab region followed by
interlization and release of the encapsulated bioactive.
anti – target monoclonal antibody anchored on
liposomes(immunoliposomes) with specific avidity to the celluler
determinants or receptors have been investigated to the drug
including idoxiuridine and acyclovir in the treatment of Herpes
simplex Virus (HVS) INFECTED CELL line.

13. Immunoconjugates
Immunoconjugates are antibodies conjugated (joined) to a second
molecule, usually a toxin, radioisotope or label. These conjugates are
used in immunotherapy and to develop monoclonal antibody
therapy as a targeted form of chemotherapy when they are often
known as antibody-drug conjugates.
the formation of antibody molecules (bispecific antibody ) ,
an enzyme (antibody-enzyme conjugated), toxins (immunotoxins),
chemotherapeutic agent(drug – conjugates), Biological modulator
such as lymphokines or growth factors.
anti-receptor (target) monoclonal antibody as well as
established for their role in tumor targeting.

14. Bispecific antibody
This is an attractive strategy for target oriented site-
specific drug delivery. The approach has been mainly
suggested for immunotherapy of immunological
disorders specially these related to lack of MHC
restricted recognition by immune effector cells.
bispecific antibody against tumors endothelium
on one hand and tissue factor ( the initiator of the
extrinsic pathway of blood conjugation ),on the other
hand have also been proposed for the synergistic effect.

15. Immunotoxins
Immunotoxins are conjugated of antibody (Mab and Fab) fragment and
toxins, in which cell binding moieties of the toxins are replaced with specific
binding chain of the antibodies. The immunotoxins may be anchored to the
surface of carrier system which provide the batter projection to them, and
effectively present and places them to recognition sites.

16. Monoclonal antibodies are attached to biologically active drugs by chemical
linkers with labile bonds. By combining the unique targeting of mAbs with the
cancer-killing ability of cytotoxic drugs, antibody-drug conjugates allow sensitive
discrimination between healthy and diseased tissue.
Drug conjugate

17. The ideal antibody-enzyme conjugate retains all the immunoreactivity and enzyme activity
of its components, has defined and appropriate proportions, and is stable. Functional
groups in the protein, such as amino, thiol, or saccharide groups, are exploited, and in
nearly all cases bifunctional reagents are used to link the enzyme to the immunoglobulin G
(IgG). The three most commonly used methods are presented here with minor
modifications to the originally described procedures.
Antibody – Enzyme conjugates

19. Radiolabeled monoclonal antibodies
• Radiolabeled antibodies have small radioactive particles attached to them.
• Ibritumomab tiuxetan is an example of a radiolabeled mAb. This is an antibody
against the CD20 antigen, which is found on lymphocytes called B cells.
• The antibody delivers radioactivity directly to cancerous B cells and can be used to
treat some types of non-Hodgkin lymphoma.
• Treatment with this type of antibody is sometimes known as radio immunotherapy
(RIT).

20. 1)Homogeneity:
Monoclonal antibody represents a single antibody molecule that binds
to antigens with the same affinity and promote the same effectors
functions.
2) Specificity:
The product of a single hybridoma reacts with the same epitope on
antigens.
3) Immunizing Antigen:
Need not be characterized and is ultimately not needed in large
quantities to produce large quantities of antibody.
4) Selection:
It is possible to select for specific epitope specificities and generate
antibodies against a wider range of antigenic determinants.
5) Antibody Production:
Advantages

21. Average affinity of monoclonal antibodies are generally lower than
polyclonal antibodies
Monoclonal against conformational epitopes on native proteins may lose
reactivity with antigens.
Antibodies sometimes display unexpected cross reactions with unrelated
antigens.
Immune rejections
Time and effort commitment: VERY LARGE.
Affinity: Average affinity of monoclonal antibodies is generally lower than
polyclonal antibodies.
Cross-reactions: Antibodies sometimes display unexpected cross-
reactions with unrelated antigens.
Disadvantages

22. Diagnostic Applications
Detects protein of interest either by blotting or
immunofluorescence
Cardiovascular diseases
Deep vein thrombosis
Location of primary and secondary metastatic
tumor's
Immunosuppressive therapy
Pregnancy testing kits
Application

23. Therapeutic Applications
Radioisotope immunoconjugates
Toxin and drug immunoconjugates
Immunoliposome based kits
In cancer

24. Reference
1. Lachman/Lieberman’s The Theory and Practice of Industrial
Pharmacy, Editors: Roop Khar, SP Vyas, Farhan Ahmad, Gaurav Jain,
Chapter 25 Targeted Drug Delivery Systems, Pg. No. 907-943,
201Andrew M. Scott1, James P.
2. Allison and Jedd D. Wolchok, Monoclonal Antibodies in Cancer
Therapy, Cancer Immunity, Vol. 12, Pg. No. 14 – 21, 2012.4.
3. Fundamentals of medical biotechnology: Author: Aparna rajagopalan,
page no: 209-253