IMMUNOTHERAPEUTICS

Dr. Pragasam Viswanathan

Professor, SBST
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.
 HISTOR
Y
William Coley, 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.
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.
 TYPES OF IMMUNOTHERAPY
The main types of
immunotherapy
now being used to treat
cancer
are:
 Monoclonal
Antibodies
 Cancer Vaccines
 Non – Specific
Immunotherapies
 Engineered
 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.
 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
 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.
  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.

 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.
 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.
 Non- Specific Immunotherapies and Adjuvants
Non- specific immunotherapies don’t target 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.
 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
 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 distinct from chimeric
 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.
 Uses of humanised Antibodies

It includes:
Reduction in the immunogenicity of an antibody
Therapeutic value of an antibody increases after
humanization.
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.
 In1891, William B. Coley (father of immunotherapy)
injected bacteria into a patient with cancer.
 Stimulated patient’s immune system and helped shrink
patients tumor.
 Increase of immune system. Counteract
strength signals by cancer cells that suppress
producedresponses.
immune
Drugs that boost the Immune system
Thalidomide
Lenalidomide
Bacille calmette- Guerin
Imiquimod.