Immunotherapeutics, types of immunotherapeutics, humanisation antibody therapy and immunotherapeutics in clinical practice by Kashikant Yadav
Size: 2.1 MB
Language: en
Added: Dec 06, 2017
Slides: 33 pages
Slide Content
DEPARTMENT OF PHARMACOLOGY CELLULAR AND MOLECULAR PHARMACOLOGY IMMUNOTHERAPEUTICS Kashikant Yadav M.pharm (Pharmacology) KARNATAKA COLLEGE OF PHARMACY
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.
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.
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 Antibodies
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.
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.
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.
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.
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 receptor ( FcRn ).
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 antibodies. It carry a larger stretch of non-human protein.
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. 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 immune responses.
Drugs that boost the Immune system Thalidomide Lenalidomide Bacille calmette - Guerin Imiquimod .
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.