Antibody's in drug delivery

1. Antibodies in drug delivery
Presented by
Saravanan subramaniyam
Department of Pharmaceutics
Faculty of Pharmacy
Sri Ramachandra University

2. INTRODUCTION
 An antibodies is a protein produced by the immune
system to identify and neutralize foreign objects like
bacteria and viruses. Each antibody recognizes a specific
antigen unique to its target.
 Antibodies are produced by a specialized group of cells
called B-Lymphocytes.

3. Monoclonal Anti-bodies
Monoclonal antibodies are mono-specific antibodies that are
made by identical immune cells that are all clones of a unique parent
cell, in contrast to polyclonal antibodies, which are made from several
different immune cells.
Monoclonal antibodies have monovalent affinity, in that they bind to
the same epitope. monoclonal antibodies that specifically bind to that
sub-stance they can serve to detect or purify that substance.
This is an important tool in biochemistry, molecular biology and
medicine.
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5. General classification
 Naked mAb
 Conjugated mAb
 Bispecific mAb
Naked Monoclonal Antibody: those without any drug or radioactive material
attached to them
 Mark the cells for the immune system
 Attach to receptors – block binding of growth factors
E.g. 1. Trastuzumab - For advanced breast cancer (HER-2)
2. Rituximab - For B cell non Hodgkin lymphoma (CD 20)
3. Cetuximab - For advanced colorectal cancer ( HER-1)
4. Bevacizumab - For metastatic colorectal cancer (VEGF)
5. Alemtuzumab - For B cell chronic lymphocytic leukemia. (CD 52)

6. Immune-conjugate:
 MAbs conjugated with chemotherapeutic agents e.g. brentuximab vedotin and
ado-trastuzumab emtansine.
 Brentuximab vedotin, attached to a chemo drug (MMAE) targets the CD30
antigen (present on T and B-cells) in treatment of Hodgkin lymphoma and non-
responding anaplastic large cell lymphoma.
 Ado-trastuzumab emtansine, attached to DM1 chemo drug, targets the HER2
protein antigen used for curing advanced breast cancer patients.

7. Bi specific monoclonal
antibodies

8. MECHANISM OF MONOCLONAL
ANTIBODY
Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme Prodrug
therapy; ADCC: antibody dependent cell-mediated cytotoxicity; CDC: complement-
dependent cytotoxicity; MAb: monoclonal antibody; scFv, single-chain Fv fragment.

9. Production of monoclonal antibody's

10. Finding solutions for Human use
• In one approach, one takes the DNA
that encodes the binding portion of
monoclonal mouse antibodies and
merges it with human antibody
producing DNA, in order to make
bacteria produce antibodies that are
half mouse and half human.

11. Production of human monoclonal antibody's
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.

12.  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 reticule endothelial system &
target tissue.
 Half-life
 Chimeric : 4 –15 days
 Humanized: 3 - 24 days
 Recombinant human: 11– 24 days
 Human anti-mouse antibody (HAMA) response develops 7–10
days following exposure to murine antibody
Pharmacokinetics: mAbs

13. Possible side effects of monoclonal
antibodies
• Allergic reactions, such as hives or itching
• Flu-like symptoms, including chills, fatigue, fever, and muscle aches and
pains
• Skin rashes
• Infusion reactions. Severe allergy-like reactions can occur and, in very few
cases, lead to death
• Dangerously low blood cell counts. Decreased red blood cells, white blood
cells and platelets
• Cardiac complications Certain monoclonal antibodies may cause heart
failure and a small risk of MI
• Bleeding. Some of the monoclonal antibody drugs are designed to stop
cancer from forming new blood vessels. There have been reports that these
medications can cause bleeding

15. Applications of Monoclonal Antibodies
 Diagnostic Applications
- Detects protein of interest either by blotting
or immunofloroscence
 Therapeutic Applications
1. Transplant rejection
2. Cancer
3. Autoimmune disorders
4. Inflammatory disease

16. Applications of Monoclonal Antibodies
• Rheumatoid arthritis
• Crohn’s disease, UC
• Psoriasis
• Ankylosing spondilosis

17. Conjugated monoclonal antibody therapy
• Toxins or radioactive isotopes
are bound to the constant region
of the MAbs.
• When the MAb binds to the
surface cells of a tumour the
toxin or radioactivity will kill the
cancer cells and all cells within
a certain radius (a killing zone).
• In this way cancer cells within
the tumour will be killed

18. Monoclonal antibodies for cancer
treatment
Possible treatment for cancer
involves monoclonal antibodies
that bind only to cancer cells
specific antigen and induce
immunological response on the
target cancer cell (naked
antibodies).
mAb can be modificated for
delivery of [toxin], radioisotope,
cytokine.

19. What is advances in monoclonal
anti-bodies

20. A Nanobodies/single-domain antibody is a peptide chain of
about 110 amino acids long, comprising one variable domain (VH) of
a heavy-chain antibody, or of a common IgG 1989 - Raymond
Hamers Discovered in camels Completely lack the light chain! Same
antigen affinity as their four- chain counterparts Structure makes
them more resistant to heat and pH May lead to development of oral
nanobodies pills Orally available single-domain antibodies against E.
coli-induced diarrhoea in piglets have been developed and
successfully tested Other diseases of the gastrointestinal tract, such
as inflammatory bowel disease and colon cancer, are also possible
targets for orally available sdAbs
Nano-bodies

21. World antibodies market
• Currently more than 200 monoclonal antibodies are in development
• Targeted disorders include cancer, heart disease, infectious diseases and
autoimmune diseases
• Market is still in its inception stage,
• Market size estimated at nearly $2.8 billion in 1999,
• Market forecast growth to almost $9.8 billion in 2004.
• Expected therapeutic antibody average annual growth rate is projected
at 21.8%
• main market is U.S. market

24.  Antigen specific, can be produced against any type of antigen,
hence vast diagnostic applications
 Target specificity, a novel therapeutic approach particularly in
cancer
 Finally, the dreams of Paul Ehrlich who considered antibodies a
magic bullets have become reality. Monoclonal antibodies have
established themselves as the most important and rapidly
expanding class of drugs in oncology. Paul Ehrlich (1854-1915)
Conclusion

26. Thank you