monoclonal antibody drugs(MAB)(Anticancer)

therapy of cancer by monoclonal antibody

1. MONOCONAL ANTI
BODY(MABs)
ANTI CANCER
Done by :Dr/ Abdulatef Abbas
Master degree in pharmacology

2. MONOCONAL ANTI BODYs(MABs)

3. MONOCONAL ANTI BODY(MAB)

Content :
1- Definition MoAbs
What are anti biodies. 2-
3- Type of anti body.
4- Type of MoAbs.
5- MABs Used to Deliver Isotopes to Tumors.
6- FDA-Approved necked (non-conjugated MoAbs)
7- Reference.

4. to specifically bind to target cells or this ) Mab:( Background
may then stimulation the pt. immune sys to attack those cells
or these are man-made versions of immune system protiens.
anti bodies can be very useful in treating cancer because they
can be designed to attack a very specific part of a cancer cell.
- experimental at mouse cells Then by recombinant
technology produce humanized anti bodies.
General of (MoAbs)

5. What are antibodies.
Anti body is a protein used by the immune system to
identify and neutralize foreign objects like bacteria and
viruses. Each anti body recognize a specific antigen unigue
to its target.
Monoconal anti body mabs are anti body that are identical
because they were produced by one type of immune cell. All
clones of a single parent cell.
Anti bodies; are anti bodies the are derived from different cell
lines. Polyclonal

6. Monoclonal antibodies
• Antibodies have important uses beyond fighting
infections in the body.
• Production of long-lasting monoclonal antibodies is a
recent invention and it is used in both medicine and
research.
• Monoclonal Antibody: a stable antibody which can be
used over a period of time

7. Monoclonal antibodies
Monoclonal antibodies (mAbs) are produced by
introducing an antigen to a mouse and then fusing
polyclonal B cells from the mouse's spleen to
myeloma cells.
The resulting hybridoma cells are cultured and
continue to produce antibodies to the antigen.

11. Producing Monoclonal Antibodies
1. Inject a mouse with a specific antigen to stimulate its
immune system to produce necessary antibodies.
2. Extract mouse spleen cells (containing Blymphocytes)
and culture them in the lab.
3. Extract mouse tumour cells, which grow continuously,
and culture them in the lab.
4. Mix spleen cells and tumour cells on the same plate
and culture.

12. Producing Monoclonal Antibodies
5. Add polyethylene glycol – this causes some B lymphocytes to
fuse with tumour cells to produce a hybrid cell called a
hybridoma.
6. Grow the cells under conditions that allow only hybridoma
cells to survive.
7. Extract the cells, culture them separately and test the medium
around each cell for the specific antibody of interest.
8. Culture the cells making the desired antibody and use as
needed.

13. Monoclonal anti bodies
MONOCLONAL ANTI BODIES TO TREAT CANCER.
The immune sys. Attacks foreign subs in the body is by making large no. of
anti bodies.
An anti body is a protein that sticks to a specific protein called an antigen.
Anti body circulate throughout the body until they find and attach to the
antigen
Once attached, they can recuit other parts of the immune sys. To destroy the
cells containing antigen

14. Monoclonal antibodies to treat cancer
• The immune system attacks foreign substances in the
body is by making large numbers of antibodies.
 • An antibody is a protein that sticks to a specific protein
called an antigen.
 • Antibodies circulate throughout the body until they find
and attach to the antigen.
 • Once attached, they can recruit other parts of the
immune system to destroy the cells containing the antigen

15. Treatment of Cancer
• Cancer cells carry specific tumour-associated antigens (TAA)
on their plasma membrane.
 • Monoclonal anti-TAA antibodies have been produced.
• Drugs which kill tumour cells or inhibit key proteins in
tumour cells are attached to monoclonal anti-TAA antibodies.
• Cancer cells are specifically targeted, avoiding damage to
healthy host cells.

21. .The type of MoAbs
1- Chimeric antibodies typically contain antigen-binding murine variable
regions and human constant regions.
2- Murine source MoAbs rodent MoAbs with excellent affinities and
specificities, generated using conventional hydrioma techno. Clinical
efficacy compromised by human anti murine anti bodies response. Which
lead to allergic or murine complex hypersensitivities.
3-chimeric MoAbs; chimers combine the human constant regions with
the intact rodent variable regions. Affinity and specificity unchange. Also
cause human anti chimeric antibodies response
(30% murine resource)
3- humanized MoAbs ; cotained only the CDRs of the rodent variable
grafted into human variable region framework.

22. Types of MoAbs
Comments Example %human Structure
Radio conjugates Tositumomab.
Ibritumomab
0 mouse
Cetuximab.
Rituximab.
65 Chimeric
Trastuzumab. 95 Humanized
Transgenic mice Panitumumab 100 human

25. The type of mAbs
A.Previous syllable
B.-tu (m) for tumor in general (ma (r)-breast ,
C.pr(o)prostate , co(i)-colon, )= tositumomab
D..ci (r)- for circulatory ; bevacizumab

26. Type monoclonal antibodies
-A Naked monoclonal antibodies;
“Naked” monoclonal antibodies, or monoclonal antibodies that work by themselves,
are the most common kind of monoclonal antibody used to treat cancer. Like all
monoclonal antibodies, they bind to specific proteins on cancer cells and rally immune
cells to their cause. One way they do this is by targeting immune system
“checkpoints,” regulators of the immune system.
Cancer has evolved to become smart enough to develop an array of escape
mechanisms to trick the immune system into ignoring it as a threat. This includes
impersonating normal body cells and exploiting checkpoint proteins such as PD-1 on T
cells in the immune system.
T cells seek out and destroy foreign invaders and cancerous cells, but PD-1 helps rein
in the T cells so that they don’t go overboard and destroy healthy cells. However,
many cancer cells wear a protein called PD-L1, which can fool T cells into treating
them as normal cells, leaving them to multiply freely. That’s where naked monoclonal
antibodies come in: They can block these checkpoint molecules, allowing T cells to
seek out and destroy the cancer cells.
Naked monoclonal antibodies can also work by latching onto antigens on cancer cells
that help cancer cells proliferate. An example of this is trastuzumab (Herceptin), which
is used to target the HER2 protein, which is sometimes found on the surface of breast
and stomach cells.

27. Type monoclonal antibodies
B-antibodies Conjugated monoclonal odies
Other monoclonal antibodies carry a radioactive substance, drug, or toxin that kills
cancer cells recognized by the antibody. These are called conjugated monoclonal
antibodies.
Antibody-drug conjugates, antibodies that have chemotherapy drugs attached to
them, target the surface of cancer cells and deliver the toxic substance to that specific
area. This approach can eliminate some of the side effects of chemotherapy, which
can damage healthy cells when used as a single agent.
Radioimmunotherapy is a treatment that uses monoclonal antibodies in combination
with radiation. By attaching a monoclonal antibody to a radioactive molecule, this
technique can deliver a dose of radiation therapy directly to tumor cells.

28. Type monoclonal antibodies

Side effects:
Monoclonal antibody therapy can result in side
effects for patients, particularly when used in
combination with other treatments. Those side
effects can include fever, chills, weakness,
headache, nausea, vomiting, diarrhea, low
blood pressure, and rashes skin

29. MABAB

30. . Monolonal anti bodies against epidermal growth factor receptor2
(EGFR-2,HER-2)
Very effective against breast cancer in which HER-2 is
“overexpressed “(more than usual amount per cell)about 20% of
all breast cancers)
Often used in combination with chemotherapy
Inhibition HER-2 mediated signalling in HER-2 +tumors
. prevent HER2 activation blocking extracellular domain cleavage
. activation antibody – depended cellular cytotoxicity.

31. Cetuximab

. Monolonal anti bodies against epidermal growth factor receptor1
(EGFR1)
. effective in colon cancer and head and neck cancer, possibly usesd in
lung cancer
. used with chemotherapy and radiation therapy.
. S.E
Can couse serious rashes in som people because target a cell protein
called EGFR which is found on normal skin cells

32. cetuximab
Monolonal anti bodies against epidermal growth factor receptor1
(EGFR1)
.effective in colon cancer and head and neck cancer, possibly usesd in
lung cancer
.used with chemotherapy and radiation therapy.
S.E
Can couse serious rashes in som people because target a cell protein
called EGFR which is found on normal skin cells.

33. Bevacizumab

. Monoclonal anti bodies against vascular endothelial growth factor
(VEGF).
Which stimulate angiogenesis (growth of new blood vessels into tumor)
. effective against cancer of colon ,lung ,breast, kidney , and brain
. combination with paclitaxel at metabolic HER2 -ve breast cancer….
. S.E
bleeding, high b.p, poor wound healing, blood clots, kidney damage

34. Ibritumomab

. is an anti-CD20 murine monoclonal antibody labeled with
isotopic yttrium ( 90Y ) or 111 In. The radiation of the isotope
coupled to the antibody provides the major antitumor activity.
Ibritumomab is approved for use in patients with relapsed or
refractory low-grade, follicular, or B-cell nonHodgkin’s
lymphoma, including patients with rituximab-refractory follicular
disease. It is used in conjunction with rituximab in a two-step
therapeutic regimen.

35. FDA-Approved nacked (non-conjugated MoAbs)
Cancer(s) Target Brand name Generic name
CLL CD52 campath Alemtuzumab
IgG1 humanized
Multiple VEGF avastin Bevacizumab
IgG1 humanized

Colon H&N EGFR1 erbitux Cetuximab
U-o-ch
Colon EGFR1 vectibix Panitumumab
Fully human IgG2 kappa light chain
Lymphomas CD20 molecule
on normal and
Lymphomasmal
ignant B
Lymphomas
rituxan Rituximab
IgG1 human fc- chimeric murine –
human
Breast HER-2 herceptin trastuzumab
Derived recombinant DNA

36. Drugs
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37. Drugs

38. Drugs

39. References
1- BASIC&CLINICAL PHARMACOLOGY 14
th

EDKatzung.
2- GOODMAN &GILMAN,S THE PHARMACOL ,
OGICAL BASIS OF THERAPUTICS -11
th
Ed.(2006)by
kabalpg.
3- Applied pharmacotherapy and therapeutic.
4- Dr /……..