Immunotherapeutics, types of immunotherapeutics, humanisation antibody therapy and immunotherapeutics in clinical practice by Kashikant Yadav

1. DEPARTMENT OF PHARMACOLOGY
CELLULAR AND MOLECULAR PHARMACOLOGY
IMMUNOTHERAPEUTICS
Kashikant Yadav
M.pharm (Pharmacology)
KARNATAKA COLLEGE OF PHARMACY

2. immunotherapy
 It is also sometimes
called biologic
therapy or
biotherapy.
 It is a treatment that
uses certain parts of
the immune system
to fight disease such
as cancer.

3. HISTORY
 William Coley, MD, a New York surgeon, first noted
that getting an infection after surgery seemed to
help some cancer patients. In the late 1800s, he
began treating cancer patients by infecting them
with certain kinds of bacteria, which came to be
known as coley toxins.
 Although he had some success, his technique was
overshadowed when other forms of cancer
treatment, such as radiation therapy, came into use.

5. How it works ?
Immunotherapy includes a wide variety of treatments
that work in
different ways.
 By boosting the body’s immune system in a very general
way.
 Helps to train the immune system to attack cancer cells
specifically.
 Giving immune system components, such as man-made
immune system proteins.

6. TYPES OF IMMUNOTHERAPY
The main types of
immunotherapy
now being used to treat
cancer
are:
 Monoclonal Antibodies
 Cancer Vaccines
 Non – Specific
Immunotherapies
 Engineered Antibodies

7. Monoclonal antibodies
 Many copies of a specific Antibody can be made in the
lab. These are known as Monoclonal Antibodies (mAbs
or moAbs).
 These Antibodies can be useful in fighting diseases
because they can designed specifically to only target a
certain antigen, such as one that is found on cancer
cells.
 Over the past 15years, the US FDA has approved
about a mAbs to treat certain cancers.

8. TYPES OF MONOCLONAL
ANTIBODIES
Two types of monoclonal antibodies are used in
cancer treatment:
 Naked mAbs are antibodies that work by themselves.
 Conjugated mAbs are those joined to a chemotherapy
drug, radioactive particles, or a toxin.
a) Radiolabeled Antibodies
b) Chemolabeled Antibodies
c) Immunotoxins

9. Naked Monoclonal Antibodies
 Naked mAbs can work in different ways. Some may
boost a person’s immune response against cancer
cells. Other work by blocking specific proteins that help
cancer cells grow ( some may do both).
 For example – Herceptin (trastuzumab) is an antibody
against the HER 2/neu protein. It is used to treat breast
and stomach cancers that have large amounts of this
protein.

11. Conjugated mAbs are also sometimes referred to as tagged,
labeled or
loaded Antibodies. They can be divided into groups
depending on what they are linked to.
 mAbs with radioactive particles attached are referred to
as radiolabeled, and treatment with this type of
Antibody is known as radioimmunotherapy (RIT).
 mAbs with chemotherapy drugs attached are referred
to as chemolabeled.
 mAbs attached to cell toxins are called immunotoxins.

13. Chemolabeled Antibodies
 These mAbs have powerful chemotherapy drugs
attached to them.
 There are only 2 chemolabeled antibodies
approved by the FDA to treat cancer at this time.

15. Side effects of Monoclonal
Antibodies
In general, the more common side effects caused by
Monoclonal
Antibody drugs include :
 Allergic reaction, such as hives or itching.
 Flu – like symptoms, including chills, fatigue, fever,
muscle aches and pains.
 Nausea
 Diarrhea
 Skin rashes.

19. Types of Cancer Treatment
Vaccines
 Tumor cell vaccines
 Antigen vaccines
 Dendritic cell vaccines
 DNA vaccines.
 Vector – based vaccines – vectors are special viruses,
bacteria, yeast cells, or other structures that can be
used to get antigens or DNA into the body.

20. Side effects of cancer vaccines
Side effects are usually mild and can include.
 Fever
 Chills
 Fatigue
 Back and joint pain
 Nausea
 Headache
A few men may have more severe symptoms, including
problems
breathing and high blood pressure.

21. Non- Specific Immunotherapies and
Adjuvants
Non- specific immunotherapies don’t target cancer cells
specifically.
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.

25. Engineered Antibodies
 Antibody engineering is used in the treatment of
numerous diseases and many diagnostic tests. It
exhibit four main effector function : antibody-dependent
cellular cytotoxicity (ADCC), phagocytosis,
complement-dependent cytotoxicity (CDC) and half-
life/clearance rate.
 Each of these effector functions is mediated through
interaction with a specific set of receptor and cell types:
ADCC and phagocytosis through interaction of cell-
bound mAbs with Fc gamma receptor , CDC through
interaction of cell- bound mAbs with the series of
soluble blood proteins that constitute the complement
system (e.g. C1q,C3,C4,etc.), and half- life/clearance
rate through binding of antibodies to the neonatal Fc

27. HUMANISATION ANTIBODY THERAPY
 Humanized antibodies
are antibodies from non-
human species whose protein
sequences have been
modified to increase their
similarity to antibody variants
produced naturally in humans.
 It can be necessary when the
process of developing a
specific antibody
involves generation in a non-
human immune system.
 Humanized antibodies are

28. Production of humanised
Antibodies
 Humanised Antibodies are
produced by grafting
murine hypervariable
amino acid domains into
human antibodies.
 This results in a molecule
of approximately 95%
human origin.

29. Uses of humanised
Antibodies
It includes:
 Reduction in the immunogenicity of an antibody
 Therapeutic value of an antibody increases after
humanization.

30. Immunotherapeutics in clinical
practice
 Von Behring and Wernicke found that animals could be
cured of diphtheria.
 An injection of sera produced by animals immunized
with an attenuated form of diphtheria successfully
treated a child with
diphtheria.
 In 1891, William B. Coley (father of immunotherapy)
injected bacteria into a patient with cancer.
 Stimulated patient’s immune system and helped shrink
patients tumor.
 Increase strength of immune system. Counteract
signals produced by cancer cells that suppress

31. Drugs that boost the Immune
system
 Thalidomide
 Lenalidomide
 Bacille calmette- Guerin
 Imiquimod.

32. Immunotherapy - A Revolution against
cancer
The promise of Immunotherapy is a cure for cancer
without the
serious side effects of chemotherapy, radiation therapy
and surgery.