Immune and prodrug therapy

1. IMMUNE THERAPY,
PRODRUG AND
TARGETED THERAPIES
Monika U
18BCHA12

2. CANCER
• Cancer is the uncontrolled proliferation abnormal cells in the
body.
There are five main categories of cancer :
1. Carcinomas begin in the skin or tissues that line the internal organs.
2. Sarcomas develop in the bone, cartilage, fat, muscle or other
connective tissues.
3. Leukemia begins in the blood and bone marrow.
4. Lymphomas start in the immune system.
5. Central nervous system cancers develop in the brain and spinal cord.

3. TREATMENT FOR CANCER
● Treatment options depend on the type of cancer, its stage (if the cancer
has spread) and general health. The goal of treatment is to kill as many
cancerous cells while minimizing damage to normal cells nearby.
The four main treatments are :
1. SURGERY : directly removing the tumor
2. CHEMOTHERAPY : using chemicals to kill cancer cells
3. RADIATION : using X-rays to kill cancer cells
4. IMMUNOTHERAPY : Boosting immune system

4. IMMUNOTHERAPY
● Immunotherapy for cancer was first introduced by ROSENBERG &
et.al, National Institute of Health, USA.
● It is a type of cancer treatment designed to boost the body's natural
defenses to fight the cancer.
● BIOLOGIC THERAPY or BIOTHERAPY.
● Cancer immunotherapy harness & enhances the innate powers of the
immune system to fight cancer.
● It represents the most promising new cancer treatment approach since
the development of the first chemotherapies in the late 1940’s.

5. ● Cancer immunotherapy today is a highly active & exciting field, with
unprecedented potential to deliver on the decades-long promise of
discovering, developing, delivering safe & effective treatments that make a
meaningful difference in the lives of patients fighting the disease.
WHY IMMUNE SYSTEM ?
● Our immune system is a collection of organs, special cells, and
substances that help protect us from infections and some other diseases.
● Immune cells and the substances travel through out our body to
protect us from germs that cause infections.
● Germs like viruses, bacteria, and parasites are like hostile, foreign armies
that are not normally found in your body.
● They try to invade your body to use host resources and result in harmful
effects.
● Our immune system is our body’s defense force.

6. • Sometimes the immune system doesn’t see the cancer cells as foreign
because the cells are not different enough from normal cells.
• Sometimes the immune system recognizes the cancer cells, but the
response might not be strong enough to destroy the cancer.
• To overcome this, researchers have found ways to help the immune
system recognize cancer cells and strengthen its response, so that
immune system will destroy them.
• Immunotherapy use immune system components such as proteins
called antibodies that are made in the lab.
• They boost the immune system once they are in the body.

7. • The antibodies themselves target certain proteins that help
cancer cells grow.
• By binding to cancer-aiding proteins, the antibodies stop cancer
cells from growing or make them die.
• These types of antibodies are also known as TARGETED THERAPY.

8. TYPES OF IMMUNOTHERAPY
• MONOCLONAL ANTIBODIES : These are INVITRO versions of
immune system proteins. Antibodies can be very useful in treating cancer
because they can be designed to attack a very specific part of a cancer cell.
• CANCER VACCINES : Vaccines are substances put into the body to start
an immune response against certain diseases. We usually think of them as
being given to healthy people to help prevent infections. But some vaccines
can help prevent or treat cancer.
• NON-SPECIFIC IMMUNOTHERAPIES : These treatments boost the
immune system in a general way, but this can still help the immune system
attack cancer cells.

9. MONOCLONAL ANTIBODIES
• One way 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 in 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.
• The copies of that antibody synthesised in the lab. These are known as
monoclonal antibodies (mAbs or moAbs).

10. • To make a monoclonal antibody, researchers first have to identify the
right antigen to attack. For cancer, this is not always easy.
• Over the past couple of decades, the US Food and Drug Administration
(FDA) has approved more than a dozen mAbs to treat certain cancers.
a. Naked Monoclonal Antibodies
Example : 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.

11. b. Radiolabeled Antibodies
Have small radioactive particles attached to them.
Eg: 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
cancerous B cells and can be used to treat some types of non-hodgkin
lymphoma.
c. Chemo Labeled Antibodies
These mAbs have powerful chemotherapy (or other) drugs attached
to them. They are also known as antibody-drug conjugates (ADCs). (The
drug is often too powerful to be used on its own – it would cause too
many side effects if not attached to an antibody.)

12. CANCER VACCINES
● Vaccines use weakened or killed germs like viruses or bacteria to start an
immune response in the body. Getting the immune system ready to
defend against these germs helps keep people from getting infections.
● Some cancer treatment vaccines are made up of cancer cells, parts of
cells, or pure antigens.
● Sometimes a patient’s own immune cells are removed and exposed to
these substances in the lab to create the vaccine. Once the vaccine is
ready, it’s injected into the body to increase the immune response against
cancer cells.

13. ● Cancer vaccines cause the immune system to attack cells with one or more
specific antigens. Because the immune system has special cells for
memory, it’s hoped that the vaccine might continue to work long after it’s
given.
● Sipuleucel-T (Provenge®) is the only vaccine approved so far by the
US Food and Drug Administration (FDA) to treat cancer. It is used to
treat advanced prostate cancer that is no longer being helped by
hormone therapy.

14. NON-SPECIFIC CANCER IMMUNOTHERAPIES & ADJUVANTS
Non-specific immunotherapies don’t target cancer cells specifically.
1. CYTOKINES
● Cytokines are chemicals made by some immune system cells.
● They are crucial in controlling the growth and activity of other
immune system cells and blood cells in the body.
● Cytokines are injected, either under the skin, into a muscle, or into a
vein. The most common ones are discussed here.

15. 2. INTERLEUKINS
● (IL-2) helps immune system cells grow and divide more quickly.
● A man-made version of IL-2 is approved to treat advanced kidney cancer
and metastatic melanoma.
3. INTERFERONS
● Interferons, first discovered in the late 1950s, help the body resist virus
infections and cancers.
● The types of interferon (IFN) are named after the first 3 letters of the
Greek alphabet: IFN-alfa, IFN-beta, and IFN- gamma.
● Only IFN-alfa is used to treat cancer. It boosts the ability of certain
immune cells to attack cancer cells.
● It may also slow the growth of cancer cells directly, as well as the blood
vessels that tumors need to grow.

16. The FDA has approved IFN-alfa for use against these cancers :
➔ Hairy cell leukemia
➔ Chronic myelogenous leukemia (CML)
➔ Follicular non-Hodgkin lymphoma
➔ Cutaneous (skin) T-cell lymphoma
➔ Kidney cancer
➔ Melanoma
➔ Kaposi sarcoma

17. PRODRUG
A prodrug is a medication or compound that, after administration,
is metabolized (i.e., converted within the body) into a pharmacologically
active drug. Inactive prodrugs are pharmacologically inactive medications
that are metabolized into an active form within the body.
For example, sulfasalazine is a prodrug.
It is not active in its ingested form.
It has to be broken down by bacteria in the colon into two
products. 5-aminosalicylic acid (5ASA) and sulfapyridine.
Before becoming active as a drug.

18. WHY PRODRUGS ARE USED ?
Prodrugs can be used to improve drug delivery or pharmacokinetics,
to decrease toxicity, or to target the drug to specific cells or tissues.
Ester and phosphate hydrolysis are widely used in prodrug design
because of their simplicity, but such approaches are relatively ineffective
for targeting drugs to specific sites.

19. TARGETED THERAPIES
Targeted therapy is the foundation of precision medicine.
It is a type of cancer treatment that targets the changes in cancer cells
that help them grow, divide, and spread.
As researchers learn more about the cell changes that drive cancer, they
are better able to design promising therapies that target these changes or block
their effects.
TYPES OF TARGETED THERAPIES
Most targeted therapies are either small-molecule drugs or monoclonal
Abs

20. Small-molecule drugs : Small enough to enter cells easily, so they are used
for targets that are inside cells.
Monoclonal antibodies, also known as therapeutic antibodies, are proteins
produced in the lab. These proteins are designed to attach to specific targets
found on cancer cells. Some monoclonal antibodies mark cancer cells so that
they will be better seen and destroyed by the immune system. Other monoclonal
antibodies directly stop cancer cells from growing or cause them to self-
destruct. Still others carry toxins to cancer cells.are drugs that are not able to
enter cells easily. Instead, they attach to specific targets on the outer surface of
cancer cells.

21. HOW DOES TARGETED THERAPY WORKS ?
Most types of targeted therapy help treat cancer by interfering with specific
proteins that help tumors grow and spread throughout the body. They
treat cancer in many different ways. They can
1. Help the immune system destroy cancer cells :
One reason that cancer cells thrive is because they are able to hide
from your immune system. Certain targeted therapies can mark cancer cells
so it is easier for the immune system to find and destroy them. Other targeted
therapies help boost your immune system to work better against cancer.

22. 2. Stop cancer cells from growing :
Healthy cells in your body usually divide to make new cells only when
they receive strong signals to do so. These signals bind to proteins on the cell
surface, telling the cells to divide. This process helps new cells form only as
your body needs them. But, some cancer cells have changes in the proteins on
their surface that tell them to divide whether or not signals are present. Some
targeted therapies interfere with these proteins, preventing them from telling
the cells to divide. This process helps slow cancer’s uncontrolled growth.

23. 3. Stop signals that help form blood vessels :
Tumors need to form new blood vessels to grow beyond a certain size. In a
process called angiogenesis, these new blood vessels form in response to
signals from the tumor. Some targeted therapies called angiogenesis
inhibitors are designed to interfere with these signals to prevent a blood
supply from forming. Without a blood supply, tumors stay small. Or, if a tumor
already has a blood supply, these treatments can cause blood vessels to die,
which causes the tumor to shrink.

24. 4. Deliver cell-killing substances to cancer cells :
Some monoclonal antibodies are combined with toxins, chemotherapy
drugs, and radiation. Once these monoclonal antibodies attach to targets on
the surface of cancer cells, the cells take up the cell-killing substances, causing
them to die. Cells that don’t have the target will not be harmed.
5. Cause cancer cell death :
Healthy cells die in an orderly manner when they become damaged or
are no longer needed. But, cancer cells have ways of avoiding this dying
process. Some targeted therapies can cause cancer cells to go through this
process of cell death.

25. 6. Starve cancer of the hormones it needs to grow :
Some breast and prostate cancers require certain hormones to grow.
Hormone therapies are a type of targeted therapy that can work in two ways.
Some hormone therapies prevent your body from making specific hormones.
Others prevent the hormones from acting on your cells, including cancer cells.

26. DRAWBACKS :
Targeted therapy does have some drawbacks. These include:
● Cancer cells can become resistant to targeted therapy. For this reason, they
may work best when used with other types of targeted therapy or with other
cancer treatments, such as chemotherapy and radiation.
● Drugs for some targets are hard to develop. Reasons include the target’s
structure, the target’s function in the cell, or both.

27. SIDE EFFECTS OF TARGETED THERAPY :
Targeted therapy can cause side effects.
The side effects you may have depend on the type of targeted therapy
you receive and how your body reacts to the therapy.
There are medicines for many of these side effects.
These medicines may prevent the side effects from happening or treat
them once they occur.
Most side effects of targeted therapy go away after treatment ends.

28. The most common side effects of targeted therapy include
1. Diarrhea and liver problems.
2. Problems with blood clotting and wound healing.
3. High blood pressure fatigue, mouth sores, nail changes, the loss of hair
color, and skin problems.
4. Skin problems might include rash or dry skin.
5. Very rarely, a hole might form through the wall of the esophagus, stomach,
small intestine, large bowel, rectum, or gallbladder.

29. How will I know whether targeted therapy is
working?
While you are receiving targeted therapy, you will see your doctor
often. He or she will give you physical exams and ask you how you feel. You
will have medical tests, such as blood tests, x-rays, and different types of scans.
These regular visits and tests will help the doctor know whether the treatment
is working.