Introduction to cancer immunotherapy using monoclonal antibodies. Understanding monoclonal antibodies in cancer therapy, manipulation of immune system to induce apoptosis on cancerous cells. Some monoclonal antibodies and their immunological mechanisms. Types of monoclonal antibodies. Riruximab, trastuzumab, cetuximab....mode of actions

1. MONOCLONAL ANTIBODIES IN
CANCER THERAPY
Moses Dumbuya

2. Introduction
• What is antibodies: 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.
• Antigens are those substance that causes production of antibodies.
•
Antibody ; an immunoglobulin, a specialized immune protein,
produced because of an introduction of an antigen into the body,
and which possesses the remarkable ability to combine with the very
antigen;.
Monoclonal antibody: an antibody produced by simple a simple
clone of cells, monoclonal antibody is therefore a single type of
antibody.

3. Structure of Antibodies
• Antibodies are glycoprotein molecules present in blood, produced against antigens. •
• Antibodies are secreted by B-lymphocytes/B-cells. Antibodies contain two regions:-
1. Variable Region 2. Constant Region.

4. Introduction
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.
Polyclonal antibodies are
antibodies that are derived from
different cell lines.

5. What mAbs are made of
Monoclonal antibodies are man-made proteins that act
like human antibodies in the immune system. There are 4
different ways they can be made and are named based on
what they are made of.
Murine: These are made from mouse proteins and the
names of the treatments end in -omab.
Chimeric: These proteins are a combination of part
mouse and part human and the names of the treatments
end in -ximab.
Humanized: These are made from small parts of mouse
proteins attached to human proteins and the names of the
treatments end in -zumab
Human: These are fully human proteins and the names of
the treatments end in -umab.

6. Types of mAbs used to treat cancer
Naked monoclonal antibodies
Naked mAbs are antibodies that have no drug or radioactive
material attached to them. They work by themselves. These are
the most common type of mAbs used to treat cancer. Most naked
mAbs attach to antigens on cancer cells, but some work by
binding to antigens on other, non-cancerous cells, or even free-
floating proteins. Naked mAbs can work in different ways.
Some boost a person’s immune response against cancer cells by
attaching to them and acting as a marker for the body’s immune
system to destroy them. An example is alemtuzumab
(Campath®), which is used to treat some patients with chronic
lymphocytic leukemia (CLL). Alemtuzumab binds to the CD52
antigen, which is found on cells called lymphocytes (which
include the leukemia cells). Once attached, the antibody attracts
immune cells to destroy these cells.

7. Other naked mAbs work mainly by attaching to and
blocking antigens on cancer cells (or other nearby
cells) that help cancer cells grow or spread. For
example, trastuzumab (Herceptin) is an antibody
against the HER2 protein. Breast and stomach cancer
cells sometimes have large amounts of this protein on
their surface. When HER2 is activated, it helps these
cells grow. Trastuzumab binds to these proteins and
stops them from becoming active.
Conjugated monoclonal antibodies
Conjugated mAbs are combined with a chemotherapy
drug or a radioactive particle. These mAbs are used as
a homing device to take one of these substances
directly to the cancer cells. The mAb circulates
throughout the body until it can find and hook onto the
target antigen.

8. Conjugated monoclonal antibodies
• .
It then delivers the toxic substance where it is needed most. This lessens the damage to
normal cells in other parts of the body. Conjugated mAbs are also sometimes referred
to as tagged, labeled, or loaded antibodies.
Radiolabeled antibodies: Radiolabeled antibodies have small radioactive particles
attached to them. Ibritumomab tiuxetan (Zevalin) 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 cancer cells. It is made of
both an mAb drug (rituximab) and a radioactive substance (Yttrium-90). Treatment
with this type of antibody is sometimes known as radioimmunotherapy (RIT).
The drug and radiation are delivered directly to the target cells because the mAb looks
for the target, then the radiation affects the target and nearby cells to a certain extent

9. Conjugated monoclonal antibodies
Chemolabeled antibodies: These mAbs have
powerful chemotherapy (or other) drugs attached
to them. Examples include:
Brentuximab vedotin (Adcetris), an antibody that
targets the CD30 antigen (found on
lymphocytes), attached to a chemo drug called
MMAE.
Ado-trastuzumab emtansine (Kadcyla, also
called TDM-1), an antibody that targets the
HER2 protein, attached to a chemo drug called
DM1.

10. How do monoclonal antibodies (MABs)
work?
• A MAB works by recognising and finding specific proteins on cells. Some
work on cancer cells, others target proteins on cells of the immune system.
• Each MAB recognises one particular protein. They work in different ways
depending on the protein they are targeting.

11. How do monoclonal antibodies (MABs) work?
• MABs work as an immunotherapy in different ways. Some MABs work in more than
one way.
• They can:
• trigger the immune system to attack and kill cancer cells
• act on cells to help the immune system attack cancer cells
Some MABs trigger the immune system to attack and kill cancer cells.
Although cancer cells are abnormal, they develop from normal cells so they can be difficult for the
immune system to spot.
Some MABs attach themselves to cancer cells, making it easier for the cells of the immune system to
find them. This process is called antibody-dependent cell-mediated cytotoxicity or ADCC.

12. trigger the immune system to attack and kill cancer
cells
ExamplesofMABSthatworkinthiswayinclude:
rituximab (Mabthera) – a treatment for chronic lymphocytic
leukaemia (CLL) and some types of non Hodgkin lymphoma
cetuximab (Erbitux) – a treatment for advanced bowel cancer
and head and neck cancer
trastuzumab (Herceptin) – used to treat breast cancer and
stomach cancer

13. Rituximab (Mabthera, Rixathon, Truxima)
• .
Rituximab is a targeted cancer drug and is also
known by its brand names MabThera, Rixathon
and Truxima.
It is a treatment for:
chronic lymphocytic leukaemia (CLL)
some types of non-Hodgkin lymphoma (NHL)
some non cancer related illnesses
You might have the original rituximab drug
called Mabthera, or a biosimilar such as
Truxima or Rixathon. A biosimilar is a very
similar copy of the original drug, but it is not
exactly the same. Biosimilars undergo strict
testing to check they work just as well as the
original drug

14. Mode of action of Riruximab
• How rituximab works
• Rituximab is a monoclonal antibody. It targets a protein
called CD20 on the surface of the leukaemia and
lymphoma cells. Rituximab sticks to all the CD20 proteins
it finds. Then the cells of the immune system pick out the
marked cells and kill them.

15. trastuzumab
Trastuzumab is a targeted cancer drug. It is a
treatment for cancers that have large amounts of a
protein called human epidermal growth factor
receptor 2 (HER2) Open a glossary item, such as:
early breast cancer (the cancer hasn't spread
beyond the breast or the lymph nodes in the
armpit on the same side of the body. So, the
cancer hasn't spread to any other part of the body)
breast, stomach and gastro oesophageal junction
cancer that has spread to another part of the body
(advanced or metastatic cancer)

16. Mode of action of trastuzumab work?
How does trastuzumab work?
Some breast and stomach cancers have large amounts of human epidermal growth factor receptor 2
(HER2). They are called HER2 positive cancers. HER2 makes the cancer cells grow and divide.
Trastuzumab is a type of targeted cancer drug called a monoclonal antibody. It works by attaching to
HER2 so it stops the cancer cells from growing and dividing.

17. Cetuximab (Erbitux)
Cetuximab is a type of targeted cancer drug. It is also known by its
brand name Erbitux. You might have it as a treatment for advanced
bowel cancer and head and neck cancers that start in the mouth and
throat.
How cetuximab works
This cancer drug quickly destroys dividing cells, such as cancer cells.
It is a type of monoclonal antibody. Monoclonal antibodies (MABs) are
copies of a single antibody. They are made in the laboratory.
Monoclonal antibodies seek out cancer cells by targeting particular
proteins on the cell surface.

18. Alemtuzumab (Campath, MabCampath)
Alemtuzumab is a type of targeted cancer drug. It’s
a treatment for some types of leukaemia and skin
lymphoma. And may be used as part of a stem cell
transplant.
What is alemtuzumab?
Alemtuzumab is a type of targeted cancer drug
called a monoclonal antibody. It is a treatment for
several cancers including:
chronic lymphoblastic leukaemia (CLL)
a rare type of leukaemia called T-cell
prolymphocytic leukaemia (T-PLL)
skin lymphoma
Doctors also use alemtuzumab as part of a stem cell
transplant to reduce the risk of a complication called
graft versus host disease (GVHD Open a glossary
item).
Alemtuzumab is pronounced A-lem-TOO-zoo-mab.

19. How does alemtuzumab work?
• Alemtuzumab is a monoclonal antibody that targets a protein called CD52 on
the surface of most types of white blood cells. The alemtuzumab sticks to all
the CD52 proteins it finds. Then the immune system picks out the marked
cells and kills them.
• Pharmacokinetics
• You usually have alemtuzumab as a drip into your bloodstream
(intravenously). You may also have it as an injection under the skin
(subcutaneously).

20. Atezolizumab (Tecentriq)
• Atezolizumab is a type of immunotherapy drug.
• This treatment is used for a number of different cancer types.
• Depending on your situation you may have atezolizumab on its
own or you might have it in combination with other drugs.
• How atezolizumab works
• Atezolizumab works by blocking a protein that stops the
immune system from working properly and attacking cancer
cells. It helps to make your immune system find and kill cancer
cells.

21. Help the immune system to attack cancer
• Other MABs work by acting on cells of the immune system. For
example, a type of immunotherapy called checkpoint inhibitors.
Checkpoint inhibitors block proteins that stop the immune
system attacking cancer cells.
• Checkpoint inhibitors block different proteins, including:
• CTLA-4 (cytotoxic T lymphocyte associated protein 4)
• PD-1 (programmed cell death protein 1)
• PD-L1 (programmed death ligand 1

22. • So you might hear these drugs named after these
checkpoint proteins – for example, CTLA-4 inhibitors, PD-
1 inhibitors and PD-L1 inhibitors.
• Examples of checkpoint inhibitors include:
• ipilimumab (Yervoy) - a treatment for advanced melanoma
• nivolumab (Opdivo)
• pembrolizumab (Keytruda)
• Nivolumab and pembrolizumab are used to treat several
different types of cancer.

23. Other monoclonal antibodies
• Other MABs work in a more targeted way. For example,
they can block signals that tell cancer cells to divide. You
can read more about this in our information about
targeted cancer drugs.
• Drugs used in cancer chemotherapy and immunotherapy
https://www.cancerresearchuk.org/about-cancer/cancer-
in-general/treatment/cancer-drugs/drugs

24. Pharmacokinetics
You usually have MAB treatment through
a drip (infusion) into a vein. There are a
few MABs you have as an injection under
the skin (subcutaneous injection).
How often you have treatment and how
many treatments you need will depend
on:
which MAB you have
the type of cancer you have
Testing
Before you have some types of MAB you
might need to have tests using some of
your cancer cells or a blood sample to
find out whether the treatment is likely to
work. These tests look for changes in
certain proteins or genes.

25. Possible side effects of monoclonal antibodies
• Monoclonal antibodies are given intravenously (injected into a
vein). The antibodies themselves are proteins, so giving them can
sometimes cause something like an allergic reaction. This is more
common while the drug is first being given. Possible side effects
can include:
• Fever
• Chills
• Weakness
• Headache
• Nausea
• Vomiting
• Diarrhea
• Low blood pressure
• Rashes

26. Possible side effects of monoclonal
antibodies
Compared with chemotherapy drugs, naked mAbs tend to have
fewer serious side effects. But they can still cause problems in
some people. Some mAbs can have side effects that are related
to the antigens they target. For example:
Bevacizumab (Avastin) is an mAb that targets a protein called
VEGF that affects tumor blood vessel growth. It can cause side
effects such as high blood pressure, bleeding, poor wound
healing, blood clots, and kidney damage.
Cetuximab (Erbitux) is an antibody that targets a cell protein
called EGFR, which is found on normal skin cells (as well as
some types of cancer cells). This drug can cause serious rashes in
some people.

27. References
• https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-
drugs/drugs/trastuzumab
• https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-
drugs/drugs/rituximab
• Monoclonal antibody difintion
• https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-
antibody/art-20047808
• Adverse effects of monoclonal antibodies
• https://www.cancerresearchuk.org/about-cancer/cancer-in-
general/treatment/immunotherapy/types/monoclonal-antibodies
• https://youtu.be/0R8fArm9dBI
• https://www.google.com/search?q=monoclonal+antibodies+in+cancer+pharmacology&r
lz=1CDGOYI_enSL1009SL1009&hl=en-
GB&biw=390&bih=669&tbm=vid&sxsrf=ALiCzsYoD4uVvmcIfMjNJ-BIR-Z5F-
BVZw%3A1660609090884&ei=QuL6YtbCNaiPlwTJtazAAw&oq=monoclonal+antibodie
s+in+cancer+phar&gs_lcp=ChBtb2JpbGUtZ3dzLXZpZGVvEAEYATIFCCEQoAEyBQgh
EKABMgUIIRCgATIFCCEQoAEyBQghEKABMggIIRAeEBYQHTIICCEQHhAWEB0yCA
ghEB4QFhAdOgQIIxAnOgYIABAeEAc6BAgAEEM6BQgAEIAEOgUIABCGAzoECCEQ
FVCEFVjrTWDCXWgAcAB4AIABowKIAfUdkgEEMi0xNZgBAKABAaoBEG1vYmlsZS1n
d3MtdmlkZW_AAQE&sclient=mobile-gws-
video#fpstate=ive&vld=cid:a836e6b9,vid:h6sGMaf6Yew,st:0

28. •Thank YOU